Trial Outcomes & Findings for Bioequivalence Study of Tacrolimus in Healthy Volunteers (NCT NCT04725682)

NCT ID: NCT04725682

Last Updated: 2023-09-21

Results Overview

Measurement of whole blood tacrolimus prior to dosing and up to 72 hours post-dose

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 67 participants
• Primary outcome timeframe: 72 hours
• Results posted on: 2023-09-21

Participant Flow

Participant milestones

Measure	Sequence 1 (TRTR) Each subject is scheduled to receive each treatment twice by the end of the study in the order of TRTR. Treatment T (Test): 1 × 1mg Test tacrolimus capsules Treatment R (Reference): 1 × 1mg RLD tacrolimus capsules Tacrolimus: a single dose of 1 mg capsule per period	Sequence 2 (RTRT) Each subject is scheduled to receive each treatment twice by the end of the study in the order of RTRT. Treatment T (Test): 1 × 1mg Test tacrolimus capsules Treatment R (Reference): 1 × 1mg RLD capsules Tacrolimus: a single dose of 1 mg capsule per period
Overall Study STARTED	33	34
Overall Study COMPLETED	23	26
Overall Study NOT COMPLETED	10	8

Reasons for withdrawal

Measure	Sequence 1 (TRTR) Each subject is scheduled to receive each treatment twice by the end of the study in the order of TRTR. Treatment T (Test): 1 × 1mg Test tacrolimus capsules Treatment R (Reference): 1 × 1mg RLD tacrolimus capsules Tacrolimus: a single dose of 1 mg capsule per period	Sequence 2 (RTRT) Each subject is scheduled to receive each treatment twice by the end of the study in the order of RTRT. Treatment T (Test): 1 × 1mg Test tacrolimus capsules Treatment R (Reference): 1 × 1mg RLD capsules Tacrolimus: a single dose of 1 mg capsule per period
Overall Study Withdrawal by Subject	7	5
Overall Study Failed to comply with the requirements	2	1
Overall Study Adverse Event	1	1
Overall Study Death	0	1

Baseline Characteristics

Bioequivalence Study of Tacrolimus in Healthy Volunteers

Baseline characteristics by cohort

Measure	All Participants n=67 Participants This is a crossover study. Participants were randomized to one of the two sequences and were to receive all interventions.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	67 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	39.0 years n=93 Participants
Sex: Female, Male Female	21 Participants n=93 Participants
Sex: Female, Male Male	46 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	65 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	52 Participants n=93 Participants
Race (NIH/OMB) White	13 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	67 participants n=93 Participants

PRIMARY outcome

Timeframe: 72 hours

Population: Participants in the PK population with available data.

Measurement of whole blood tacrolimus prior to dosing and up to 72 hours post-dose

Outcome measures

Measure	Tacrolimus (Generic) n=62 Participants 1 x 1 mg Tacrolimus capsule (Test)	Tacrolimus (Brand) n=61 Participants 1 x 1 mg Tacrolimus capsule (Reference)
Area Under the Concentration (AUC 72)	37434.51 pg.h/mL Standard Deviation 20086.16	33716.80 pg.h/mL Standard Deviation 19885.62

PRIMARY outcome

Timeframe: 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.25, 2.50, 2.75, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00, 144.00 hours

Population: Participants in the PK population with available data.

Measurement of whole blood tacrolimus prior to dosing and up to 144 hours post-dose

Outcome measures

Measure	Tacrolimus (Generic) n=62 Participants 1 x 1 mg Tacrolimus capsule (Test)	Tacrolimus (Brand) n=62 Participants 1 x 1 mg Tacrolimus capsule (Reference)
Maximum Plasma Concentration (Cmax)	6780.05 pg/mL Standard Deviation 2830.05	4246.68 pg/mL Standard Deviation 2243.37

SECONDARY outcome

Timeframe: 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.25, 2.50, 2.75, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00, 144.00 hours

Population: Participants in the PK population with available data.

Measurement of whole blood tacrolimus prior to dosing and up to 144 hours post-dose

Outcome measures

Measure	Tacrolimus (Generic) n=62 Participants 1 x 1 mg Tacrolimus capsule (Test)	Tacrolimus (Brand) n=62 Participants 1 x 1 mg Tacrolimus capsule (Reference)
Time at Maximum Plasma Concentration (Tmax)	1.00 hour Interval 0.5 to 2.75	1.50 hour Interval 0.75 to 4.03

SECONDARY outcome

Timeframe: Estimated using the last measurable concentration (144 hours)

Population: Participants in the PK population with available data.

Time curve from time zero to infinity, calculated as AUCt + Clast/λ, where Clast is the last measurable concentration. Measurement of whole blood tacrolimus prior to dosing and up to 144 hours post-dose.

Outcome measures

Measure	Tacrolimus (Generic) n=61 Participants 1 x 1 mg Tacrolimus capsule (Test)	Tacrolimus (Brand) n=58 Participants 1 x 1 mg Tacrolimus capsule (Reference)
Area Under the Concentration (AUC Inf)	45484.38 pg.h/mL Standard Deviation 25524.52	42764.68 pg.h/mL Standard Deviation 25066.88

SECONDARY outcome

Timeframe: To the last measurable concentration or last sampling time t, whichever occurs first. (0 to 144 hours post-dose)

Population: Participants in the PK population with available data.

Area under the concentration-time curve from time zero until the last measurable concentration or last sampling time t, whichever occurs first.

Outcome measures

Measure	Tacrolimus (Generic) n=61 Participants 1 x 1 mg Tacrolimus capsule (Test)	Tacrolimus (Brand) n=58 Participants 1 x 1 mg Tacrolimus capsule (Reference)
Area Under the Concentration (AUC 0-t)	41480.11 pg.h/mL Standard Deviation 24938.47	38744.54 pg.h/mL Standard Deviation 23985.82

Adverse Events

Tacrolimus (Generic)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Tacrolimus (Brand)

Serious events: 1 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Measure	Tacrolimus (Generic) n=66 participants at risk 1 x 1 mg Tacrolimus capsule (Test)	Tacrolimus (Brand) n=64 participants at risk 1 x 1 mg Tacrolimus capsule (Reference)
General disorders Death	0.00% 0/66 • Approximately 2 months Safety population included all dosed participants.	1.6% 1/64 • Number of events 1 • Approximately 2 months Safety population included all dosed participants.

Other adverse events

Measure	Tacrolimus (Generic) n=66 participants at risk 1 x 1 mg Tacrolimus capsule (Test)	Tacrolimus (Brand) n=64 participants at risk 1 x 1 mg Tacrolimus capsule (Reference)
Nervous system disorders Headache	10.6% 7/66 • Approximately 2 months Safety population included all dosed participants.	7.8% 5/64 • Approximately 2 months Safety population included all dosed participants.
Gastrointestinal disorders Toothache	0.00% 0/66 • Approximately 2 months Safety population included all dosed participants.	3.1% 2/64 • Approximately 2 months Safety population included all dosed participants.
General disorders Vessel puncture site pain	0.00% 0/66 • Approximately 2 months Safety population included all dosed participants.	3.1% 2/64 • Approximately 2 months Safety population included all dosed participants.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.0% 2/66 • Approximately 2 months Safety population included all dosed participants.	0.00% 0/64 • Approximately 2 months Safety population included all dosed participants.
Vascular disorders Hypertension	1.5% 1/66 • Approximately 2 months Safety population included all dosed participants.	3.1% 2/64 • Approximately 2 months Safety population included all dosed participants.

Additional Information

Wei-Jhe Sun, Ph.D.

FDA/CDER/OGD

Phone: 301-796-6176

Email: ORSHSR@fda.hhs.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place