AZA: Bioequivalence of Azathioprine Suspension 10 mg/mL (Jayempi) Versus Azathioprine Tablet 50mg (Imurek®)

• Sponsor: Nova Laboratories Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03930264
• Collaborator: Medicines Evaluation Unit Ltd (Industry), Syne Qua Non Limited (Industry), Alderley Analytical Ltd (Other), Black County Pathology Services (Other), Diamond Pharma Services Regulatory Affairs Consultancy (Other), Boyd Consultants (Other)
• Enrollment: 30
• Locations: 2
• Arms: 2
• Actual Duration (Months): 1.6
• Patients Per Site: 15
• Patients Per Site Per Month: 9.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Therapeutic Equivalency	Drug: Azathioprine 50Mg Tab; Drug: Azathioprine 10mg/mL oral suspension	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Other
• Official Title: A Single Centre, Two Period Crossover Study to Assess the Bioequivalence of an Oral Azathioprine Suspension 10 mg/mL (Jayempi™) Versus Oral Azathioprine Tablet 50mg (Imurek®) in at Least 30 Healthy Adult Subjects Under Fasting Conditions
• Actual Study Start Date: Apr 11, 2019
• Actual Primary Completion Date: May 24, 2019
• Actual Study Completion Date: May 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Imurek®, 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	Drug: Azathioprine 50Mg Tab; tablet; Other Names: Imurek
Experimental: Jayempi™ 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	Drug: Azathioprine 10mg/mL oral suspension; oral suspension; Other Names: Jayempi

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [18 hours]

   The maximum (peak) plasma concentration assesses the rate of drug absorption

2. AUC0-t [18 hours]

   Area under the curve time=0 hours to t hours

3. AUC0-∞ [18 hours]

   Area under to curve from time=0 hours to infinity

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nova Laboratories Limited	Leicester	Leicestershire	United Kingdom	LE184YL
2	Medicines Evaluation Unit Ltd Southmoor Road	Manchester		United Kingdom	M23 9QZ

Sponsors and Collaborators

• Nova Laboratories Limited
• Medicines Evaluation Unit Ltd
• Syne Qua Non Limited
• Alderley Analytical Ltd
• Black County Pathology Services
• Diamond Pharma Services Regulatory Affairs Consultancy
• Boyd Consultants

Investigators

• Principal Investigator: Naimat Khan, MD, Medicines Evaluation Unit

Study Documents (Full-Text)

• Study Protocol - May 3, 2019
• Statistical Analysis Plan - May 24, 2019

More Information

Publications

None provided.

• Responsible Party: Nova Laboratories Limited
• ClinicalTrials.gov Identifier: NCT03930264
• Other Study ID Numbers: INV691
• First Posted: Apr 29, 2019
• Last Update Posted: Jun 22, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Azathioprine

Study Results

Participant Flow

Recruitment Details	Cross Over

Arm/Group Title	Imurek®, First	Jayempi™ First
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	15	15
COMPLETED	15	14
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Imurek®, First	Jayempi™, First	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	15	15	30
Age (years) [Mean (Standard Deviation) ]
Age	40.8 (9.00)	33.5 (9.61)	37 (9.88)
Sex: Female, Male (Count of Participants)
Female	5 33.3%	6 40%	11 36.7%
Male	10 66.7%	9 60%	19 63.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 6.7%	1 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 13.3%	2 6.7%
White	15 100%	12 80%	27 90%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	The maximum (peak) plasma concentration assesses the rate of drug absorption
Time Frame	18 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imurek	Jayempi™
Arm/Group Description	Tablet formulation	Liquid formulation
Measure Participants	29	29
Mean (Standard Deviation) [ng/mL]	15.49 (67.1)	17.35 (54.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Imurek, Jayempi™
	Comments
	Type of Statistical Test	Equivalence
	Comments	For bioequivalence, the 90% CIs of the geometric mean ratio of Cmax for tablet and suspension were required to be within the 80 to 125% range.
Statistical Test of Hypothesis	p-Value	0.3008
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 90%; 0.93 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUC0-t
Description	Area under the curve time=0 hours to t hours
Time Frame	18 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imurek	Jayempi™
Arm/Group Description	Tablet formulation	Liquid formulation
Measure Participants	29	29
Mean (Standard Deviation) [h.ng/mL]	17.10 (33.8)	18.17 (32.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Imurek, Jayempi™
	Comments
	Type of Statistical Test	Equivalence
	Comments	For bioequivalence, the 90% CIs of the geometric mean ratio of AUC0-τ for tablet and suspension were required to be within the 80 to 125% range.
Statistical Test of Hypothesis	p-Value	0.1061
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 90%; 1.00 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	AUC0-∞
Description	Area under to curve from time=0 hours to infinity
Time Frame	18 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imurek	Jayempi™
Arm/Group Description	Tablet formulation	Liquid formulation
Measure Participants	23	26
Mean (Standard Deviation) [h.ng/mL]	17.71 (27.1)	18.96 (31.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Imurek, Jayempi™
	Comments
	Type of Statistical Test	Equivalence
	Comments	For bioequivalence, the 90% CIs of the geometric mean ratio of AUC0-∞ for tablet and suspension were required to be within the 80 to 125% range.
Statistical Test of Hypothesis	p-Value	0.5696
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 90%; 0.96 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	AEs were collected up to the end of the follow-up period (up to 10 days after Treatment period 2) and over a total period of 2 months.
Arm/Group Title	Imurek®		Jayempi™
Arm/Group Description	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		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
All Cause Mortality
	Imurek®		Jayempi™
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Imurek®		Jayempi™
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Imurek®		Jayempi™
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)		0/30 (0%)
Nervous system disorders
Headache	2/30 (6.7%)	2	0/30 (0%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.