A Bioequivalence Study of SKF101804 Cefixime Versus Cefixime Reference Formulation in Healthy Adults Under Fasting Conditions

NCT03329547 | Withdrawn Phase 1

• 1 other identifier: 205732
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Infections, Bacterial

Keywords

Bioequivalence; Pharmacokinetics; SKF101804; Crossover; Cefixime

Outcome Measures

Primary Outcomes (4)

• Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC [0-t]) of cefixime test capsule

  Blood samples will be collected for pharmacokinetic analysis of cefixime test capsules under fasting conditions.

  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

• AUC (0-t) of cefixime reference capsule

  Blood samples will be collected for pharmacokinetic analysis of cefixime reference capsules under fasting conditions.

  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

• Maximum observed concentration (Cmax) of cefixime test capsule

  Blood samples will be collected for pharmacokinetic analysis of cefixime test capsules under fasting conditions.

  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

• Cmax of cefixime reference capsule

  Blood samples will be collected for pharmacokinetic analysis of cefixime reference capsules under fasting conditions.

  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

Secondary Outcomes (16)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Subjects receiving treatment sequence AB

EXPERIMENTAL

Eligible subjects will receive treatment sequence AB; A= SKF101804 cefixime 400 mg test capsules and B= cefixime 400 mg reference capsules. Subjects will receive single oral dose of treatment A in treatment period 1 on Day 1 and treatment B in treatment period 2 on Day 1. Treatment periods 1 and 2 will be separated by a washout period of 7 to 14 days.

Drug: Cefixime test capsule; Drug: Cefixime reference capsule

Subjects receiving treatment sequence BA

EXPERIMENTAL

Eligible subjects will receive treatment sequence BA; B= cefixime 400 mg reference capsules and A= SKF101804 cefixime 400 mg test capsules. Treatment periods 1 and 2 will be separated by a washout period of 7 to 14 days. Subjects will receive single oral dose of treatment B in treatment period 1 on Day 1 and A in treatment period 2 on Day 1. Treatment periods 1 and 2 will be separated by a washout period of 7 to 14 days.

Drug: Cefixime test capsule; Drug: Cefixime reference capsule

Interventions

Cefixime test capsule DRUG

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.

Subjects receiving treatment sequence AB; Subjects receiving treatment sequence BA

Cefixime reference capsule DRUG

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.

Subjects receiving treatment sequence AB; Subjects receiving treatment sequence BA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
• Any other condition that is capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
• Abnormal renal function, as determined by creatinine clearance and considered as clinically significant by the investigator will be excluded.
• Abnormal blood pressure as determined by the investigator.
• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Breast cancer within the past 10 years.
• ALT \>1.5x upper limit of normal (ULN).
• Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of colitis.
• History of cephalosporin induced hemolytic anemia.
• QT interval corrected for heart rate according to Bazett's formula (QTcB) \>450 milliseconds (msec). Subjects with a known risk of QT prolongation will be excluded.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Bacterial Infections

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This will be an open-label study. Hence, masking will not be provided.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: January 11, 2018
• Primary Completion: February 2, 2018
• Study Completion: February 2, 2018
• Last Updated: March 7, 2018

Record last verified: 2018-03