Renal Replacement TherapiesPhase 1COLCHINCALNCT01160276
Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients
A Phase 1 study testing cyclosporine+colchicine and tacrolimus in people with Renal Replacement Therapies, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Ciclosporin inhibits P-glycoprotein should increase colchicine bioavailability whereas tacrolimus should not influence colchicine disposition. This is a prospective, controlled, open labeled study performed in renal graft recipients comparing colchicine single dose (1mg) pharmacokinetics in 14 patients treated with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Replacement Therapies
- What is being tested?
- cyclosporine+colchicine and tacrolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteFrance
- Study dates
- May 2010to Jan 2012
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with renal graft since at least 1 year
- Patients treated with ciclosporin or tacrolimus
- Are at least 18 years old.
- Glomerular filtration rate above 30 ml / min calculated using the MDRD formula
- Among the 14 patients receiving ciclosporin:
- The genotype is not a criterion for inclusion
Show all 13Show fewer
- Among the 14 patients with tacrolimus treatment:
- 7 genotype ABCB1 3435CC, 7 genotype ABCB1 3435TT
- Recent (1 month) residual concentration of tacrolimus between 5-10ng/ml
- Recent (1 month) residual concentration of ciclosporin between 100-200ng/ml
- For women : a negative pregnancy test (serum beta hCG)
- Realization of a medical examination.
- Informed consent and writing form.
Who cannot join
- Abnormal transaminases (AST and ALT above the ULN Laboratory).
- Underlying Liver Disease (steatosis, cirrhosis, chronic hepatitis, the virus of hepatitis C or B).
- Previous history of muscle disease (drug related especially the statin type).
- Leukopenia (WBC <3000/mm3).
- Hemoglobin <11g/dl.
- Patient treated by erythropoetin (whatever its hemoglobin value).
Show all 19Show fewer
- Abnormal CPK (greater than the ULN Laboratory).
- Prior intolerance to colchicine.
- Regular intake of the following medications associated with rhabdomyolyses: antipsychotics, cholesterol lowering agents (statins or fibrates), zidovudine, antidepressants (selective inhibitor of serotonin reuptake) and lithium.
- Patient (e) can not refrain from consuming grapefruit juice.
- Patient (e) taking a tea based on St John's wort.
- Taking drugs inducers of P-gp or CYP3A4 (rifabutin, rifampin, carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, protease inhibitors, griseofulvin).
- Taking drugs inhibitors of P-gp or CYP3A4 (quinidine, macrolide antibiotics, azole antifungals, protease inhibitors, amiodarone, diltiazem, verapamil).
- Chronic diarrhea.
- ABCB1 Genotype 3435CT for patients in the tacrolimus group.
- Participation in another concurrent trial.
- Patient (e) exclusion period of another trial.
- Patient (e) having reached the maximum annual amount of compensation provided by law.
- No affiliation to French social security scheme or without CMU.
Trial locations and contacts
1 site in 1 country.
France1 site
Assistance publique - Hôpitaux de Paris : Bicêtre Hospital
Le Kremlin-Bicêtre, 94275
About this study
Official title: An Open Non Randomized Comparative Study Exploring Drug Interaction Between Colchicine and Calcineurin Inhibitors in 2 Groups (Ciclosporin Group and Tacrolimus Group) of Renal Graft Recipients
Ciclosporin inhibits P-glycoprotein should increase colchicine bioavailability whereas tacrolimus should not influence colchicine disposition.
This is a prospective, controlled, open labeled study performed in renal graft recipients comparing colchicine single dose (1mg) pharmacokinetics in 14 patients treated with tacrolimus and 14 patients treated with cyclosporin.
Read the detailed description
- Renal transplantation >= one year
- eGFR (MDRD) > 30ml/min
- hemoglobin >= 11g/dl
- treatment with tacrolimus or cyclosporine
- no previous muscular disease
- no drugs interfering with P-glycoprotein or CYP3A activity or expression outcomes
- colchicine AUC, Cmax, T1/2
- ABCB1C3435T, CYP3A5 and SLCO1B1 genotypes
- Conditions
- Renal Replacement Therapies
- Being tested
- cyclosporine+colchicine, tacrolimus
- Keywords
- renal graft, colchicine, drug interaction, cyclosporine, tacrolimus, renal transplantation, renal transplant, ABCB1, CYP3A5, SLCO1B1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclosporine+colchicineDrug
Also called Colchicine, Colchimax
the 14 patients of the 1st group are under cyclosporine and One pill of colchimax 1mg will be taken by all the patients at Day 3.
tacrolimusDrug
Also called Colchicine, Colchimax
the 14 patients of the second group are under tacrolimus and One pill of colchimax 1mg will be taken by all the patients at Day 3.
| Study group | Role | What they receive |
|---|---|---|
| Cyclosporine | Active comparator | The first group is composed of 14 renal graft recipients under cyclosporine Receives: Drug: cyclosporine+colchicine |
| Tacrolimus | Active comparator | The second group is composed of 14 renal graft recipients under tacrolimus Receives: Drug: tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve of plasma concentration of colchicine over time 0-∞
Measured: 4 weeks
Secondary outcomes (10)
Half-life of colchicine (T1/2).
Measured: 4 weeks
AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp)
Measured: 4 weeks
Cmax observed colchicine.
Measured: 4 weeks
Residual tacrolimus or cyclosporine concentrations
Measured: 4 weeks
ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group.
Measured: 4 weeks
ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T.
Measured: 4 weeks
CYP3A5 Genotype: search for the allele * 1 (rs 776746): 3 possible genotypes CYP3A5 * 3 / * 3 - CYP3A5 * 3 / * 1 - CYP3A5 * 1 / * 1.
Measured: 4 weeks
GFR calculated by MDRD formula.
Measured: 4 weeks
BMI
Measured: 4 weeks
Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII)
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2010 (estimated)
- Study startMay 2010
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Replacement TherapiesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antoine Jacquet, MD, Principal investigator, Nephrology Department of BICETRE Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01160276
- Sponsor's protocol ID
- P081105
- Acronym
- COLCHINCAL
- Status last verified
- Apr 2013
- First submitted
- 9 Jul 2010
- Last updated
- 11 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Non Randomized Comparative Study Exploring Drug Interaction Between Colchicine and Calcineurin Inhibitors in 2 Groups (Ciclosporin Group and Tacrolimus Group) of Renal Graft Recipients
- ClinicalTrials.gov ID
- NCT01160276
- Acronym / sponsor ID
- COLCHINCAL / P081105
- Conditions
- Renal Replacement Therapies
- Keywords
- renal graft, colchicine, drug interaction, cyclosporine, tacrolimus, renal transplantation, renal transplant, ABCB1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- May 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 12 Jul 2010 (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.
Ciclosporin inhibits P-glycoprotein should increase colchicine bioavailability whereas tacrolimus should not influence colchicine disposition.
This is a prospective, controlled, open labeled study performed in renal graft recipients comparing colchicine single dose (1mg) pharmacokinetics in 14 patients treated with tacrolimus and 14 patients treated with cyclosporin.
Detailed description
- Renal transplantation >= one year
- eGFR (MDRD) > 30ml/min
- hemoglobin >= 11g/dl
- treatment with tacrolimus or cyclosporine
- no previous muscular disease
- no drugs interfering with P-glycoprotein or CYP3A activity or expression outcomes
- colchicine AUC, Cmax, T1/2
- ABCB1C3435T, CYP3A5 and SLCO1B1 genotypes
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclosporine | Active comparator | Drug: cyclosporine+colchicineThe first group is composed of 14 renal graft recipients under cyclosporine |
| Tacrolimus | Active comparator | Drug: tacrolimusThe second group is composed of 14 renal graft recipients under tacrolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with renal graft since at least 1 year
- Patients treated with ciclosporin or tacrolimus
- Are at least 18 years old.
- Glomerular filtration rate above 30 ml / min calculated using the MDRD formula
- Among the 14 patients receiving ciclosporin:
Key exclusion criteria (19 listed)
- Abnormal transaminases (AST and ALT above the ULN Laboratory).
- Underlying Liver Disease (steatosis, cirrhosis, chronic hepatitis, the virus of hepatitis C or B).
- Previous history of muscle disease (drug related especially the statin type).
- Leukopenia (WBC <3000/mm3).
- Hemoglobin <11g/dl.
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 |
|---|---|---|
| cyclosporine+colchicineAlso: Colchicine, Colchimaxthe 14 patients of the 1st group are under cyclosporine and One pill of colchimax 1mg will be taken by all the patients at Day 3. | Drug | Cyclosporine |
| tacrolimusAlso: Colchicine, Colchimaxthe 14 patients of the second group are under tacrolimus and One pill of colchimax 1mg will be taken by all the patients at Day 3. | Drug | Tacrolimus |
Primary outcome
Area under the curve of plasma concentration of colchicine over time 0-∞
Time frame: 4 weeks
10 secondary outcomes
Half-life of colchicine (T1/2).
Time frame: 4 weeks
AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp)
Time frame: 4 weeks
Cmax observed colchicine.
Time frame: 4 weeks
Residual tacrolimus or cyclosporine concentrations
Time frame: 4 weeks
ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group.
Time frame: 4 weeks
ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T.
Time frame: 4 weeks
CYP3A5 Genotype: search for the allele * 1 (rs 776746): 3 possible genotypes CYP3A5 * 3 / * 3 - CYP3A5 * 3 / * 1 - CYP3A5 * 1 / * 1.
Time frame: 4 weeks
GFR calculated by MDRD formula.
Time frame: 4 weeks
BMI
Time frame: 4 weeks
Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII)
Time frame: 4 weeks
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 11 Apr 2013.
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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.
Antoine Jacquet, MD principal investigator
Nephrology Department of BICETRE Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cyclosporine+colchicine and tacrolimus in people with Renal Replacement Therapies, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 13 inclusion and 19 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 11 Apr 2013. 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 France. 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 curve of plasma concentration of colchicine over time 0-∞ (time frame: 4 weeks). 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 11 Apr 2013.