Therapeutic Equivalency
Conditions
Brief summary
A single center, single dose, open-label, randomized, two period crossover study to assess the bioequivalence of an oral azathioprine suspension 10 mg/mL (Jayempi™) versus oral azathioprine tablet 50mg (Imurek®, Aspen Pharma Trading Limited, Dublin, Ireland.) in at least 30 healthy adult subjects under fasting conditions.
Detailed description
This will be a single-dose, open-label, randomised, two-period crossover study with orally administered 1 x 5mL (50 mg) of Jayempi™ Oral Suspension 10mg/mL versus oral azathioprine tablet 50mg (Imurek®, Aspen Pharma Trading Limited, Dublin, Ireland) on two separate occasions conducted under fasting conditions in healthy male and female subjects at a single study centre. The study will comprise: * Thiopurine methyltransferase (TPMT) testing; * Screening period of maximum 28 days * Two treatment periods (each of which will include a PK profile period of 12 hours) separated by a wash-out period of at least 3 calendar days (minimum number of days based on half-life of the analyte) and maximum of 14 calendar days between consecutive administrations of the IMP * A post-study visit 7-10 days after the last dose of the last treatment period of the study. Subjects will be randomly assigned to treatment sequence, prior to the first administration of IMP.
Interventions
DRUGAzathioprine 50Mg Tab
tablet
DRUGAzathioprine 10mg/mL oral suspension
oral suspension
Sponsors
Medicines Evaluation Unit Ltd
Syne Qua Non Limited
Alderley Analytical Ltd.
Black County Pathology Services
Diamond Pharma Services Regulatory Affairs Consultancy
Boyd Consultants
Nova Laboratories Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Volunteers. * No significant medical history or conditions that may interfere with the study. * Adequate contraception.
Exclusion criteria
* Volunteers who may be likely to have the inherited mutated NUDT15. * Subjects with a deficient, low or intermediate TPMT enzyme activity. * Disease that may interfere with the safety of the participant or the study outcome measures. * Participants who want to procreate in the next 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | 18 hours | The maximum (peak) plasma concentration assesses the rate of drug absorption |
| AUC0-t | 18 hours | Area under the curve time=0 hours to t hours |
| AUC0-∞ | 18 hours | Area under to curve from time=0 hours to infinity |
Countries
United Kingdom
Participant flow
Recruitment details
Cross Over
Participants by arm
| Arm | Count |
|---|---|
| Imurek®, First Generic name : Azathioprine Trade name : Imurek® 50mg tablet Dosage form : Tablet containing 50 mg azathioprine Dose : 1 x Imurek 50mg Tablet per treatment period under fasting conditions Mode of administration : Orally Manufacturer : Aspen Pharma Trading Limited, Dublin, Ireland Country of origin : Ireland
Azathioprine: tablet | 15 |
| Jayempi™, First Generic name : Azathioprine
Trade name : (Jayempi™) 10 mg/ mL Oral solution Dosage form : Oral suspension containing 10 mg/mL Azathioprine Dose : 1 x 5mL (50 mg) of Jayempi™ Oral Suspension 10mg/mL per treatment period under fasting conditions Mode of administration : Orally Manufacturer : Nova Laboratories Ltd. Country of origin : Leicester, UK
Azathioprine: oral suspension | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Jayempi™, First | Total | Imurek®, First |
|---|---|---|---|
| Age, Continuous Age | 33.5 years STANDARD_DEVIATION 9.61 | 37 years STANDARD_DEVIATION 9.88 | 40.8 years STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 27 Participants | 15 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 19 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 2 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
AUC0-∞
Area under to curve from time=0 hours to infinity
Time frame: 18 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imurek | AUC0-∞ | 17.71 h.ng/mL | Standard Deviation 27.1 |
| Jayempi™ | AUC0-∞ | 18.96 h.ng/mL | Standard Deviation 31.6 |
p-value: 0.569690% CI: [0.96, 1.09]ANOVA
Primary
AUC0-t
Area under the curve time=0 hours to t hours
Time frame: 18 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imurek | AUC0-t | 17.10 h.ng/mL | Standard Deviation 33.8 |
| Jayempi™ | AUC0-t | 18.17 h.ng/mL | Standard Deviation 32.1 |
p-value: 0.106190% CI: [1, 1.13]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax)
The maximum (peak) plasma concentration assesses the rate of drug absorption
Time frame: 18 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imurek | Maximum Observed Plasma Concentration (Cmax) | 15.49 ng/mL | Standard Deviation 67.1 |
| Jayempi™ | Maximum Observed Plasma Concentration (Cmax) | 17.35 ng/mL | Standard Deviation 54.4 |
p-value: 0.300890% CI: [0.93, 1.35]ANOVA