Bioequivalence Study of Albendazole 400 mg Tablets in Chinese Population

A Single-dose, Two-centre, Randomized, Open-label, Two-way Crossover Bioequivalence Study of Two Kinds of AlbendazoleTablet Formulations in Healthy Chinese Adult Males

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01755637

Enrollment

Registered

2012-12-24

Start date

2012-04-30

Completion date

2012-06-30

Last updated

2013-07-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Helminthiasis

Brief summary

The purpose of the study is to compare the pharmacokinetic profiles of two Albendazole tablet formulations manufactured under the different granulation processes in healthy Chinese adult males.

Detailed description

Due to the product manufacture process change in Albendazole oral formulation from ethanol based granulation process to aqua based granulation process, State Food and Drug Administration officially requested Tianjin Smith Kline and French Laboratories to carry out a Bioequivalence study to demonstrate bioequivalence between the manufacturing processes. This trial will be conducted to support the official requirement via the comparison of the pharmacokinetic profiles between both the drugs manufactured under the different processes. After oral administration, Albendazole is quickly oxidized into its pharmacologically active metabolite, Albendazole sulphoxide (ABZ-SO. Due to extensive metabolism and limited absorption, plasma concentration of ABZ after oral administration was found to be too low to be measured. Thus, this trial will also compare the pharmacokinetic profiles of ABZ-SO manufactured using different solvents.

Interventions

DRUGAlbendazole

Albendazole tablets 400 mg

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 40 Years

Healthy volunteers

Yes

Inclusion criteria

1. Male aged from 18 years up to 40 years (inclusive). 2. Body mass index within the range of 19-24kg/m\^2. 3. Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or physical examination. 4. Negative for serum hepatitis B surface antigen, hepatitis C antibody and antibody of HIV.

Exclusion criteria

1. Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. 2. Substance abuse: Recent history (within the last year) of alcohol or other substance abuse or failed to pass drugs of abuse screen and/or alcohol screen test. 3. Disease 1. Current or recurrent disease that could affect the action, absorption or distribution of the study medication or clinical or laboratory assessments (e.g. hepatic disorders, abnormal liver function tests, renal insufficiency, congestive heart failure); 2. Current or relevant previous history of serious, severe or unstable physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures; 3. History of gastrointestinal bleeding or peptic ulcer; 4. Asthma 5. History of liver disease 4. Medication 1. Use of any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to dosing 2. Current or regular use of any prescription or over-the-counter medication, any other ABZ containing products, and traditional Chinese medicine. 5. Smoking 1. Subjects who are current smokers or non-smokers of less than 3 months; 2. Prior (within seven days of dosing) or current use of any other nicotine containing products, including nicotine replacement therapy. 6. Blood 1. Blood donation ≥ 500 ml within 90 days before the first study session. 2. Plasma donation within the 90 days before the first study session.

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] of Albendazole.	Blood samples were collected pre-dose 0 hour (hr) and post dose 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr	AUC (0-t) was evaluated using the trapezoid rule.
AUC [0-infinity (Inf)] of Albendazole	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr	AUC (0-inf) was evaluated using the trapezoid rule.
Maximum Observed Plasma Concentration [Cmaximum (Max)] of Albendazole	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr	Cmax was depicted from plasma concentration of Albendazole.

Secondary

Measure	Time frame	Description
Time to Reach Maximum Plasma Concentration (Tmax) of Albendazole	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr	Tmax was time at which Cmax of Albendazole was reached.
Cmax of Active Metabolite - Albendazole Sulphoxide	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr	Cmax was depicted from plasma concentration of Albendazole.
AUC (0-t) of Active Metabolite - Albendazole Sulphoxide	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr	AUC (0-t) of Albendazole i.e. Albendazole sulphoxide was evaluated using the trapezoid rule.
AUC (0-inf) of Active Metabolite - Albendazole Sulphoxide	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr	AUC (0-inf) of Albendazole sulphoxide was evaluated using the trapezoid rule.

Countries

China

Participant flow

Recruitment details

Study was conducted at two clinical sites in China.

Pre-assignment details

Out of 123 screened participants, 54 did not meet the study criteria; 12 withdrew consent and one was lost to follow -up. Only 56 participants were randomized.

Participants by arm

Arm	Count
All Randomized Participants All randomized participants were evaluated for baseline measures	56
Total	56

Withdrawals & dropouts

Period	Reason	FG000	FG001
Period 1	Adverse Event	0	1

Baseline characteristics

Characteristic	All Randomized Participants
Age Continuous	24.21 Years STANDARD_DEVIATION 2.715
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	56 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 55	4 / 56
serious Total, serious adverse events	0 / 55	0 / 56

Outcome results

Primary

Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] of Albendazole.

AUC (0-t) was evaluated using the trapezoid rule.

Time frame: Blood samples were collected pre-dose 0 hour (hr) and post dose 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr

Population: The analysis was carried out per protocol population. Missing data was not imputed for evaluation.

Arm	Measure	Value (MEAN)	Dispersion
Experimental: Albendazole Tablet (Aqua Based)	Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] of Albendazole.	54.82 nanogram (ng).hr per milliliter (mL)	Standard Deviation 51.56
Reference: Albendazole Tablet (Alcohol Based)	Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] of Albendazole.	48.07 nanogram (ng).hr per milliliter (mL)	Standard Deviation 49.22

Comparison: The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.90% CI: [100.49, 130.16]

Primary