Clinical trial NCT03408392: Bioequivalence Study Between SKF101804 Cefixime 200 Milligram (mg)/5 Milliliter (mL) Suspension Versus Cefixime 200 mg/5 mL Suspension Reference Product in Healthy Adult Subjects Under Fasting Conditions
Official title: An Open-label, Randomised, Single-dose, Two-period Cross-over Study to Evaluate Bioequivalence of SKF101804 Cefixime 200 mg/5 mL Suspension Versus Cefixime 200 mg/5 mL Suspension Reference Product in Healthy Adult Participants Under Fasting Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Infections, Bacterial
Keywords: Single dose
Oral suspension
Bioequivalence
Cefixime
Two-way crossover
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2018-01-24
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study is open-label, randomized two-way cross-over study to determine if cefixime 200 mg/5 mL powder for suspension (test formulation: SKF101804) is bioequivalent to cefixime 200 mg/5 mL suspension reference formulation. Study will be conducted in 28 healthy adult subjects under fasting conditions. There will be two treatment periods and each subject will participate in both periods. The washout period between both treatment periods will be 7-14 days. Subjects will be randomized to either of treatment sequences of reference followed by test or test followed by reference to receive a single dose of test or reference formulation on Day 1 in each treatment period. The study will last for 5 to 7 weeks.


Eligibility criteria: Inclusion Criteria:

* Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
* Subject must be 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.
* Subject with a body weight 50 kilogram (kg) and body mass index (BMI) within the range 19-30 kilogram per meter square (kg/m\^2) (inclusive).
* A healthy 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, 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.
* A subject should be capable of giving signed informed consent.

Exclusion Criteria:

* Subject with 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.
* Subjects with 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.
* Subject with abnormal renal function, as determined by creatinine clearance and considered as clinically significant by the investigator will be excluded.
* Subject with abnormal blood pressure (BP) as determined by the investigator.
* Subject with 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.
* Subject who had breast cancer within the past 10 years.
* ALT \>1.5 times upper limit of normal (ULN).
* Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Subject with current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Subject with history of colitis
* Subject with 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.
* Past or intended use of over-the-counter or prescription medication including herbal medications, within 14 days prior to dosing unless in the opinion of the investigator and sponsor, the medication will not interfere with the study.
* Participation in the study would result in loss of blood or blood products in excess of 500 mL within 90 days.
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Current enrolment or past participation within the last 90 days before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
* Presence of Hepatitis B surface antigen (HBsAg) at screening. Positive Hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
* Positive pre-study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV) antibody test.
* Regular use of known drugs of abuse.
* Subjects with regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Subjects with urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
* Subjects who are sensitive to heparin or heparin-induced thrombocytopenia.
* Subjects with known sensitivity to any drugs from the class of cephalosporin, or components thereof.
* Subjects with known sensitivity to any drugs from the class of penicillin, or components thereof.
* Subjects with known sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Primary outcomes:
measure: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments (AUC [0-t]) for Cefixime
timeFrame: 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 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period
measure: Maximum Observed Plasma Concentration (Cmax) Within a Participant Across All Treatments of Cefixime
timeFrame: 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 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period
Secondary outcomes:
measure: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to (AUC [0-infinity]) Across All Treatments for Cefixime
timeFrame: 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 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period
measure: Time of Occurrence of Cmax (Tmax) for Cefixime
timeFrame: 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 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period
measure: Percentage of AUC(0-infinity) Obtained by Extrapolation (%AUCex) for Cefixime
timeFrame: 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 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period
measure: Terminal Phase Half-life (T1/2) for Cefixime
timeFrame: 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 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period
measure: Number of Participants With Non-serious Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to Day 16 in each treatment period
measure: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), and Aspartate Aminotransferase (AST) at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Blood Urea Nitrogen (BUN) at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Calcium, Glucose, Potassium and Sodium at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Total Bilirubin (Total Bil), Direct Bilirubin (Direct Bil) and Creatinine (Creat) at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Total Protein at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Mean Corpuscular Volume (MCV) at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Erythrocyte Count at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Hematocrit at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Percent Reticulocytes at Indicated Time-points
timeFrame: Day -1 and Day 2 of each treatment period
measure: Number of Participants With Potential Clinical Importance (PCI) Abnormal Findings for Urinalysis
timeFrame: Day -1 and Day 2 of each treatment period
measure: Respiratory Rate at Indicated Time-points
timeFrame: Day 1 Pre-dose 1.5 hours, Day 1 post-dose 2, 4, and 6 hours and Day 2 post-dose 24 hours of each treatment period
measure: Pulse Rate at Indicated Time-points
timeFrame: Day 1 Pre-dose 1.5 hours, Day 1 post-dose 2, 4, and 6 hours and Day 2 post-dose 24 hours of each treatment period
measure: Body Temperature at Indicated Time-points
timeFrame: Day 1 Pre-dose 1.5 hours, Day 1 post-dose 2, 4, and 6 hours and Day 2 post-dose 24 hours of each treatment period
measure: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points
timeFrame: Day 1 Pre-dose 1.5 hours, Day 1 post-dose 2, 4, and 6 hours and Day 2 post-dose 24 hours of each treatment period
Other outcomes:
Locations:
city: Bloemfontein
country: South Africa
facility: GSK Investigational Site
state: Free State
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: