Trial Outcomes & Findings for Pharmacokinetics of Sublingual Versus Oral Tacrolimus in Patients Awaiting Kidney Transplantation (NCT NCT00629122)
NCT ID: NCT00629122
Last Updated: 2019-06-12
Results Overview
Trough concentration
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
5 participants
Primary outcome timeframe
Day 3 and Day 8, time 0 (before tacrolimus dose)
Results posted on
2019-06-12
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|---|
|
First Period: Day 1- 3 (Sublingual)
STARTED
|
2
|
3
|
|
First Period: Day 1- 3 (Sublingual)
COMPLETED
|
2
|
3
|
|
First Period: Day 1- 3 (Sublingual)
NOT COMPLETED
|
0
|
0
|
|
Second Period: Day 3-5 (Washout)
STARTED
|
2
|
3
|
|
Second Period: Day 3-5 (Washout)
COMPLETED
|
2
|
3
|
|
Second Period: Day 3-5 (Washout)
NOT COMPLETED
|
0
|
0
|
|
Third Period: Day 6-8 (Oral)
STARTED
|
2
|
3
|
|
Third Period: Day 6-8 (Oral)
COMPLETED
|
2
|
3
|
|
Third Period: Day 6-8 (Oral)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics of Sublingual Versus Oral Tacrolimus in Patients Awaiting Kidney Transplantation
Baseline characteristics by cohort
| Measure |
Arm A (Tacrolimus and Nystatin)
n=2 Participants
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)
n=3 Participants
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
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 3 and Day 8, time 0 (before tacrolimus dose)Trough concentration
Outcome measures
| Measure |
Arm A (Tacrolimus and Nystatin)
n=2 Participants
Sublingual 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 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)
n=3 Participants
Sublingual 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 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).
|
|---|---|---|
|
C0 (ng/mL)
Day 3 (Sublingual)
|
1.45 ng/mL
Interval 0.1 to 2.8
|
6.2 ng/mL
Interval 3.0 to 8.3
|
|
C0 (ng/mL)
Day 8 (Oral)
|
1.25 ng/mL
Interval 0.2 to 2.3
|
6.5 ng/mL
Interval 3.2 to 11.2
|
PRIMARY outcome
Timeframe: Day 3 and Day 8, at time of maximum concentrationMaximum concentration (ng/mL)
Outcome measures
| Measure |
Arm A (Tacrolimus and Nystatin)
n=2 Participants
Sublingual 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 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)
n=3 Participants
Sublingual 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 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).
|
|---|---|---|
|
Cmax
Day 3 (Sublingual)
|
9.6 ng/mL
Interval 2.0 to 17.2
|
14.0 ng/mL
Interval 6.5 to 22.5
|
|
Cmax
Day 8 (Oral)
|
4.6 ng/mL
Interval 3.2 to 6.0
|
19.5 ng/mL
Interval 10.1 to 19.8
|
PRIMARY outcome
Timeframe: Day 3 and Day 8, time of maximum concentrationTime to Maximum concentration (hours)
Outcome measures
| Measure |
Arm A (Tacrolimus and Nystatin)
n=2 Participants
Sublingual 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 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)
n=3 Participants
Sublingual 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 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).
|
|---|---|---|
|
Tmax
Day 3 (Sublingual)
|
1.75 hours
Interval 1.5 to 2.0
|
3.0 hours
Interval 1.5 to 4.0
|
|
Tmax
Day 8 (Oral)
|
0.875 hours
Interval 0.75 to 1.0
|
2.0 hours
Interval 2.0 to 4.0
|
PRIMARY outcome
Timeframe: Day 3 and Day 8, calculated based on concentrations measured between hours 0 and 6Area Under the Concentration-Time Curve from 0-6 hours (mg-hr/L)
Outcome measures
| Measure |
Arm A (Tacrolimus and Nystatin)
n=2 Participants
Sublingual 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 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)
n=3 Participants
Sublingual 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 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).
|
|---|---|---|
|
Estimated AUC 0-6
Patient 1 Sublingual (day 3)
|
9.3 mg-hr/L
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
|
Estimated AUC 0-6
Patient 1 Oral (day 8)
|
4.9 mg-hr/L
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
|
Estimated AUC 0-6
Patient 2 Sublingual (day 3)
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
27.2 mg-hr/L
|
|
Estimated AUC 0-6
Patient 2 Oral (day 8)
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
32.4 mg-hr/L
|
|
Estimated AUC 0-6
Patient 3 Sublingual (day 3)
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
66.0 mg-hr/L
|
|
Estimated AUC 0-6
Patient 3 Oral (day 8)
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
76.0 mg-hr/L
|
|
Estimated AUC 0-6
Patient 4 Sublingual (day 3)
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
63.7 mg-hr/L
|
|
Estimated AUC 0-6
Patient 4 Oral (day 8)
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
52.5 mg-hr/L
|
|
Estimated AUC 0-6
Patient 5 Sublingual (day 3)
|
63.0 mg-hr/L
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
|
Estimated AUC 0-6
Patient 5 Oral (day 8)
|
23.2 mg-hr/L
|
NA mg-hr/L
The patient did not receive that combination (ie. was in other arm)
|
PRIMARY outcome
Timeframe: Day 3, minutes to powder dissolutionTacrolimus Powder Dissolution Time during Sublingual Administration (minutes)
Outcome measures
| Measure |
Arm A (Tacrolimus and Nystatin)
n=2 Participants
Sublingual 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 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)
n=3 Participants
Sublingual 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 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).
|
|---|---|---|
|
Tacrolimus Powder Dissolution Time
|
2.25 minutes
Interval 2.0 to 2.5
|
2.0 minutes
Interval 1.5 to 3.0
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: We were unable to assess genotype polymorphisms due to the small number of subjects enrolled in the study.
Impact of drug interaction between tacrolimus and clotrimazole troche vs. nystatin suspension. Evaluate genotype polymorphisms that influence CYP3A4, CYP3A5, and p-glycoprotein expression to determine impact on sublingual and oral tacrolimus delivery.
Outcome measures
Outcome data not reported
Adverse Events
Arm A (Tacrolimus + Nystatin)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Arm B (Tacrolimus + Clotrimazole)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm A (Tacrolimus + Nystatin)
n=2 participants at risk
Sublingual 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 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 + Clotrimazole)
n=3 participants at risk
Sublingual 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 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).
|
|---|---|---|
|
Gastrointestinal disorders
Bitter taste in mouth
|
100.0%
2/2 • Number of events 2
|
100.0%
3/3 • Number of events 3
|
Additional Information
Meredith J. Aull, Pharm.D.
Weill Cornell Medical College
Phone: (212) 746-8720
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place