Clinical trial NCT01755637: Bioequivalence Study of Albendazole 400 mg Tablets in Chinese Population
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Helminthiasis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-12-24
Enrollment: 56
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] of Albendazole.
timeFrame: 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
measure: AUC [0-infinity (Inf)] of Albendazole
timeFrame: 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
measure: Maximum Observed Plasma Concentration [Cmaximum (Max)] of Albendazole
timeFrame: 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 outcomes:
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Albendazole
timeFrame: 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
measure: AUC (0-t) of Active Metabolite - Albendazole Sulphoxide
timeFrame: 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
measure: AUC (0-inf) of Active Metabolite - Albendazole Sulphoxide
timeFrame: 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
measure: Cmax of Active Metabolite - Albendazole Sulphoxide
timeFrame: 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
Other outcomes:
Locations:
city: Beijing
country: China
facility: Central Hospital of China Aerospace Corporation
state: Beijing
city: Wuhan
country: China
facility: Tongji Hospital, Medical College Huazhong
state: Hubei
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: