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

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.

Study Overview

• Status: Completed
• Conditions: Helminthiasis
• Intervention / Treatment: Drug: Albendazole

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100049
      • Central Hospital of China Aerospace Corporation
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Medical College Huazhong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Albendazole tablet (Aqua Based); Albendazole tablets 400 milligram (mg) manufactured under aqua based solvent condition taken orally with 200 millilitre (mL) of water as single dose treatment.	Drug: Albendazole; Albendazole tablets 400 mg
Active Comparator: Albendazole tablet (Alcohol Based); Albendazole tablets 400 mg manufactured under ethanol based solvent condition taken orally with 200 mL of water as single dose treatment.	Drug: Albendazole; Albendazole tablets 400 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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-infinity (Inf)] of Albendazole	AUC (0-inf) was evaluated using the trapezoid rule.	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
Maximum Observed Plasma Concentration [Cmaximum (Max)] of Albendazole	Cmax was depicted from plasma concentration 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reach Maximum Plasma Concentration (Tmax) of Albendazole	Tmax was time at which Cmax of Albendazole was reached.	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 Active Metabolite - Albendazole Sulphoxide	AUC (0-t) of Albendazole i.e. Albendazole sulphoxide was evaluated using the trapezoid rule.	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 Active Metabolite - Albendazole Sulphoxide	AUC (0-inf) of Albendazole sulphoxide was evaluated using the trapezoid rule.	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 of Active Metabolite - Albendazole Sulphoxide	Cmax was depicted from plasma concentration 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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: December 19, 2012
• First Submitted That Met QC Criteria: December 19, 2012
• First Posted (Estimate): December 24, 2012

Study Record Updates

• Last Update Posted (Estimate): July 15, 2013
• Last Update Submitted That Met QC Criteria: July 11, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Parasitic Diseases; Helminthiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Albendazole
• Other Study ID Numbers: O7921353