Bioequivalence Study of Albendazole 400 mg Tablets in Chinese Population

• ClinicalTrials.gov Identifier: NCT01755637
• Recruitment Status: Completed
• First Posted: December 24, 2012
• Results First Posted: July 15, 2013
• Last Update Posted: July 15, 2013
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Helminthiasis	Drug: Albendazole	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-dose, Two-centre, Randomized, Open-label, Two-way Crossover Bioequivalence Study of Two Kinds of AlbendazoleTablet Formulations in Healthy Chinese Adult Males
• Study Start Date: April 2012
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: June 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] of Albendazole. [ 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 ]
   AUC (0-t) was evaluated using the trapezoid rule.
2. AUC [0-infinity (Inf)] of Albendazole [ Time Frame: 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.
3. Maximum Observed Plasma Concentration [Cmaximum (Max)] of Albendazole [ Time Frame: 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 Outcome Measures :

1. Time to Reach Maximum Plasma Concentration (Tmax) of Albendazole [ Time Frame: 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.
2. AUC (0-t) of Active Metabolite - Albendazole Sulphoxide [ Time Frame: 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.
3. AUC (0-inf) of Active Metabolite - Albendazole Sulphoxide [ Time Frame: 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.
4. Cmax of Active Metabolite - Albendazole Sulphoxide [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

China, Beijing

Central Hospital of China Aerospace Corporation

Beijing, Beijing, China, 100049

China, Hubei

Tongji Hospital, Medical College Huazhong

Wuhan, Hubei, China, 430030

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01755637
• Other Study ID Numbers: O7921353
• First Posted: December 24, 2012
• Results First Posted: July 15, 2013
• Last Update Posted: July 15, 2013
• Last Verified: May 2013

Additional relevant MeSH terms:

Helminthiasis; Parasitic Diseases; Albendazole; Anthelmintics; Antiparasitic Agents; Anti-Infective Agents; Anticestodal Agents; Antiplatyhelmintic Agents; Antiprotozoal Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents