Infections, Bacterial
Conditions
Keywords
Bioequivalence, Pharmacokinetics, SKF101804, Crossover, Cefixime
Brief summary
Cefixime is an orally active third generation cephalosporin indicated for the treatment of acute exacerbations of chronic bronchitis, acute otitis media, uncomplicated acute cystitis and uncomplicated pyelonephritis. Cefixime acts by inhibiting the action of proteins involved in the synthesis of bacterial cell walls, which leads to bacterial cell lysis and cell death. Due to lack of bioequivalence between tablet/capsule and suspension formulation of cefixime, consideration needs to be given if the oral suspension is to be substituted for the tablet/capsule. This study is designed to assess whether test SKF101804 cefixime 400 milligrams (mg) capsule is bioequivalent to reference cefixime 400 mg capsule under fasting conditions in healthy adults. Subjects will be randomized in crossover manner to receive single oral doses of treatment A (SKF101804 cefixime test capsules) and treatment B (reference cefixime capsules), followed by a washout period of 7-14 days. Approximately 26 subjects will be included in the study and total duration in the study for each subject will be approximately 5 to 7 weeks.
Interventions
DRUGCefixime test capsule
SKF101804/cefixime test capsule will be given with a single dose of 400 mg administered orally along with 240 mL of water. It will be available as a dark purple head and off white body locking type capsule with GSK' printed on cap and 400MG printed on body of capsule.
DRUGCefixime reference capsule
Cefixime reference capsule will be given with a single dose of 400 mg administered orally along with 240 mL of water. It will be available as red/orange hard gelatin size 0 capsule with Cefspan 400 mg printed on body of capsule.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
This will be an open-label study. Hence, masking will not be provided.
Intervention model description
This will be a two-period crossover study. Subjects will receive single oral dose of cefixime 400 mg test capsules and cefixime 400 mg reference capsules in treatment period 1 and 2 under fasting conditions.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent. * Healthy, non-smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the normal reference range for the population being studied may be included at investigator discretion in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight within \>=50 kilogram (kg) and body mass index (BMI) within the range 19-30 kg per meter square (kg/m\^2) (inclusive). * Healthy male or female subjects. A male subject must agree to use contraception during the treatment period and for at least 5 days after the last dose of study treatment and refrain from donating sperm during this period; a female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment. * Capable of giving signed informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC [0-t]) of cefixime test capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime test capsules under fasting conditions. |
| AUC (0-t) of cefixime reference capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime reference capsules under fasting conditions. |
| Maximum observed concentration (Cmax) of cefixime test capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime test capsules under fasting conditions. |
| Cmax of cefixime reference capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime reference capsules under fasting conditions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of AUC (0-infinity) obtained by extrapolation (percent AUCex) of cefixime test capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime test capsule under fasting conditions. |
| Percent AUCex obtained by extrapolation of cefixime reference capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime reference capsules under fasting conditions. |
| Apparent terminal phase half-life (T1/2) of cefixime test capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime test capsule under fasting conditions. |
| T1/2 of cefixime reference capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime reference capsules under fasting conditions. |
| Number of subjects with adverse events (AEs) | Up to 27 days | An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. |
| Number of subjects with serious AEs (SAEs) | Screening and up to 27 days | Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. |
| AUC from time zero extrapolated to infinite time (AUC [0-infinity]) of cefixime test capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime test capsules under fasting conditions. |
| Number of subjects with abnormal biochemistry laboratory parameters as a measure of safety | Up to 27 days | Biochemistry parameters will be analyzed including blood urea nitrogen (BUN), fasting glucose, potassium, creatinine, sodium, calcium, aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase, total and direct bilirubin and total protein as a measure of safety. |
| Number of subjects with abnormal values for body temperature | Up to 27 days | Body temperature will be measured in a semi-supine position after at least a 5-min rest. |
| Number of subjects with abnormal pulse rate | Up to 27 days | Pulse rate will be measured in a semi-supine position after 5-min rest. |
| Number of subjects with abnormal respiratory rate | Up to 27 days | Respiratory rate will be measured in a semi-supine position after at least a 5-min rest. |
| Number of subjects with abnormal values for blood pressure | Up to 27 days | Systolic and diastolic blood pressure will be measured in a supine position after 5 minutes rest. |
| Number of subjects with abnormal hematology laboratory parameters as a measure of safety | Up to 27 days | Hematology parameters will be analyzed including platelet count, red blood cells (RBC) count, hemoglobin and hematocrit level as a measure of safety. |
| AUC(0-infinity) of cefixime reference capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime reference capsules under fasting conditions. |
| Time of occurrence of Cmax (Tmax) of cefixime test capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime test capsules under fasting conditions. |
| Tmax of cefixime reference capsule | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 20.0 and 24.00 hours post dose | Blood samples will be collected for pharmacokinetic analysis of cefixime reference capsules under fasting conditions. |
Outcome results
None listed