Bioequivalence Study Between GR37547 500 Milligrams (mg) Tablet Versus Ciprofloxacin 500 mg Tablet Reference Product in Healthy Adult Subjects
Condition: Infections, Bacterial
MeSH terms: Bacterial Infections
Intervention: GR37547 tablet; Ciprofloxacin reference tablet
Intervention description: A single tablet of GR37547 should be taken orally with 240 mL of water. GR37547 500 mg tablet will be a white to off white capsule shape with break line on upper side and embossed "GSK500"on lower side.; A single tablet of ciprofloxacin reference should be taken orally with 240 mL of water. Ciprofloxacin 500 mg reference will be nearly white to slightly yellowish film coated oblong tablets with break line and ''CIP 500" marked on upper side and "BAYER" on lower side.
Intervention MeSH terms: Ciprofloxacin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Crossover assignment: Subjects will receive treatment in one of the two sequences; Treatment A (GR37547 tablet) followed by Treatment B (ciprofloxacin reference tablet) or vice versa separated by a washout period of at least 7 days and not more than 14 days.
Masking: None (Open Label)
Masking description: This will be an open-label study. Hence, masking will not be performed.
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: GR37547; Cross-over; Bioequivalence; Ciprofloxacin

Summary:

      This two-period cross-over study will evaluate bioequivalence of GR37547 (ciprofloxacin 500
      mg) tablet versus ciprofloxacin 500 mg reference tablet in healthy adult subjects under
      fasting conditions. Subjects will receive Treatment A (GR37547 tablet) and Treatment B
      (ciprofloxacin reference tablet) in crossover manner, separated by a washout period of at
      least 7 days and not more than 14 days. The total duration of study for each subject will be
      approximately 5-7 weeks. This study will enroll approximately 26 healthy adult subjects at a
      single center.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be between 18 and 60 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 only if the
             investigator 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 >=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: Male 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; Female
             subjects: 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.

          -  The investigator is responsible for ensuring that male and female study subjects
             understand how to correctly use the methods of contraception.

          -  Capable of giving signed informed consent.

        Exclusion Criteria:

          -  History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
             endocrine, hematological, neuromuscular, psychiatric, auto-immune or neurological
             disorders.

          -  History of convulsions.

          -  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.

          -  History of any malignancies or chemotherapy/radiation within the past 5 years
             excluding treated squamous carcinoma of the skin and adequately excised basal cell
             carcinoma.

          -  History of kidney, heart or lung transplants.

          -  History or presence of rheumatoid arthritis.

          -  Presence of hypocalcaemia where the serum potassium is < lower limit of normal (LLN).

          -  Presence of hypomagnesaemia where the serum magnesium is < LLN.

          -  Fasting blood glucose >=7 millimoles (mmol)/liter (L).

          -  Serum glucose-6-phosphate dehydrogenase < LLN.

          -  Abnormal renal function, as determined by creatinine clearance and considered as
             clinically significant by the investigator will be excluded.

          -  Alanine transaminase (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%).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  Excessive alkalinity of the urine (potential of hydrogen [pH] >=9), as determined on
             Day -1.

          -  Abnormal BP as determined by the investigator.

          -  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.
             For purposes of data analysis, only QTcB, will be used

          -  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.

          -  Where participation in the study would result in loss of blood or blood products in
             excess of 500 milliliter (mL) within 90 days.

          -  Exposure to more than 4 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.

          -  Presence of Hepatitis B surface antigen (HBsAg) at screening or a Positive Hepatitis C
             antibody test result at screening.

          -  Positive pre-study drug/alcohol screen.

          -  Positive human immunodeficiency virus (HIV) antibody test.

          -  Regular use of known drugs of abuse.

          -  Sensitivity to heparin or heparin-induced thrombocytopenia.

          -  Sensitivity to any of the study treatments, or components thereof, or drug or other
             allergy including allergy to quinolones that, in the opinion of the investigator or
             medical monitor, contraindicates participation in the study.

          -  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 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125
             mL) of wine or 1 (25 mL) measure of spirits.

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco or
             nicotine-containing products within 6 months prior to screening.