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Pharmacokinetics of Sublingual Versus Oral Tacrolimus in Patients Awaiting Kidney Transplantation

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ClinicalTrials.gov Identifier: NCT00629122
Recruitment Status : Completed
First Posted : March 5, 2008
Results First Posted : December 11, 2017
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):
Meredith Aull, Weill Medical College of Cornell University

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Health Services Research
Condition: Kidney Failure, Chronic
Interventions: Drug: Tacrolimus (Arm B)
Drug: Clotrimazole Troche
Drug: Tacrolimus (Arm A)
Drug: Nystatin Suspension

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm A (Tacrolimus and Nystatin)

Sublingual (SL) tacrolimus 2 mg every 12 hours (subject weight < 90 kg) or 3 mg every 12 hours (subject weight > 90kg) (study day 1 - 3). Tacrolimus capsules will be opened and the contents placed under the participants tongue. Oral (PO) tacrolimus at same dose every 12 hours (study day 6 - 8). Tacrolimus capsules will be administered by mouth. Nystatin suspension 5 mL every 12 hours (study days 1 - 3 and 6 - 8).

Study day 1: Initiate SL tacrolimus and nystatin suspension x 5 doses. Study day 3: Collection of pharmacokinetic parameters around 5th SL tacrolimus dose.

Study day 3: Start washout period, no drug administration (tacrolimus, nystatin).

Study day 5: End washout period. Study day 6: Initiate PO tacrolimus and nystatin suspension x 5 doses. Study day 8: Collection of pharmacokinetic parameters around the 5th PO tacrolimus dose.

Study day 15: Participants will be contacted by telephone to assess for any adverse effects.

Arm B (Tacrolimus and Clotrimazole)

Sublingual (SL) tacrolimus 1 mg every 12 hours (subject weight < 90 kg) or 2 mg every 12 hours (subject weight > 90 kg) (study day 1 - 3). Tacrolimus capsules will be opened and the contents placed under the participants tongue. Oral (PO) tacrolimus at same dose every 12 hours (study day 6 - 8). Tacrolimus capsules will be administered by mouth. Clotrimazole troche 10 mg every 12 hours (study day 1 - 3 and 6 - 8).

Study day 1: Initiate SL tacrolimus and clotrimazole troche x 5 doses. Study day 3: Collection of pharmacokinetic parameters around the 5th SL tacrolimus dose.

Study day 3: Start washout period, no drug administration (tacrolimus, clotrimazole).

Study day 5: End washout period.

Study day 6: Initiate PO tacrolimus and clotrimazole troche x 5 doses. Study day 8: Collection of pharmacokinetic parameters around the 5th PO tacrolimus dose.

Study day 15: Participants will be contacted by telephone to assess for any adverse effects.


Participant Flow for 3 periods

Period 1:   First Period: Day 1- 3 (Sublingual)
    Arm A (Tacrolimus and Nystatin)   Arm B (Tacrolimus and Clotrimazole)
STARTED   2   3 
COMPLETED   2   3 
NOT COMPLETED   0   0 

Period 2:   Second Period: Day 3-5 (Washout)
    Arm A (Tacrolimus and Nystatin)   Arm B (Tacrolimus and Clotrimazole)
STARTED   2   3 
COMPLETED   2   3 
NOT COMPLETED   0   0 

Period 3:   Third Period: Day 6-8 (Oral)
    Arm A (Tacrolimus and Nystatin)   Arm B (Tacrolimus and Clotrimazole)
STARTED   2   3 
COMPLETED   2   3 
NOT COMPLETED   0   0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm A (Tacrolimus and Nystatin) Sublingual (SL) tacrolimus 2 mg every 12 hours (subject weight < 90 kg) or 3 mg every 12 hours (subject weight > 90kg) (study day 1 - 3). Tacrolimus capsules will be opened and the contents placed under the participants tongue. Oral (PO) tacrolimus at same dose every 12 hours (study day 6 - 8). Tacrolimus capsules will be administered by mouth. Nystatin suspension 5 mL every 12 hours (study days 1 - 3 and 6 - 8).
Arm B (Tacrolimus and Clotrimazole) Sublingual (SL) tacrolimus 1 mg every 12 hours (subject weight < 90 kg) or 2 mg every 12 hours (subject weight > 90 kg) (study day 1 - 3). Tacrolimus capsules will be opened and the contents placed under the participants tongue. Oral (PO) tacrolimus at same dose every 12 hours (study day 6 - 8). Tacrolimus capsules will be administered by mouth. Clotrimazole troche 10 mg every 12 hours (study day 1 - 3 and 6 - 8).
Total Total of all reporting groups

Baseline Measures
   Arm A (Tacrolimus and Nystatin)   Arm B (Tacrolimus and Clotrimazole)   Total 
Overall Participants Analyzed 
[Units: Participants]
 2   3   5 
Age 
[Units: Participants]
Count of Participants
     
<=18 years      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      1  50.0%      1  33.3%      2  40.0% 
>=65 years      1  50.0%      2  66.7%      3  60.0% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      1  50.0%      1  33.3%      2  40.0% 
Male      1  50.0%      2  66.7%      3  60.0% 
Region of Enrollment 
[Units: Participants]
     
United States   2   3   5 


  Outcome Measures

1.  Primary:   C0 (ng/mL)   [ Time Frame: Day 3 and Day 8, time 0 (before tacrolimus dose) ]

2.  Primary:   Cmax   [ Time Frame: Day 3 and Day 8, at time of maximum concentration ]

3.  Primary:   Tmax   [ Time Frame: Day 3 and Day 8, time of maximum concentration ]

4.  Primary:   Estimated AUC 0-6   [ Time Frame: Day 3 and Day 8, calculated based on concentrations measured between hours 0 and 6 ]

5.  Primary:   Tacrolimus Powder Dissolution Time   [ Time Frame: Day 3, minutes to powder dissolution ]

6.  Secondary:   Drug Interactions and Genotypes   [ Time Frame: 2 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Small sample size; variable absorption profile; poor vascular access in some subjects; possible enteral absorption of sublingual drug; unable to assess genotype polymorphisms due to the small number of subjects.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Meredith J. Aull, Pharm.D.
Organization: Weill Cornell Medical College
phone: (212) 746-8720
e-mail: mea9008@med.cornell.edu



Responsible Party: Meredith Aull, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00629122     History of Changes
Other Study ID Numbers: 0710009492
First Submitted: February 12, 2008
First Posted: March 5, 2008
Results First Submitted: July 9, 2015
Results First Posted: December 11, 2017
Last Update Posted: December 11, 2017