A single dose, 3-way cross-over study comparing the safety, tolerability and pharmacokinetics of two inhaled Liposomal Ciprofloxacin Hydrochloride (HCl) for Inhalation formulations in two different nebulizers in healthy adults, with single dose assessment in subjects with non-Cystic Fibrosis (CF) bronchiectasis.

Exclusion Criteria96

• Healthy subjects must not have any of the following:
• Participation in another clinical trial within 30 days of screening visit or receipt of an
• experimental therapy within 30 days prior to dosing
• Donation >450 ml of blood within 8 weeks of first treatment dose
• Recent (1 year) history of drug or alcohol dependence
• Positive screening test for Human immunodeficiency virus (HIV) antibodies, Hepatitis B surface antigen or Hepatitis C
• antibody
• Known or suspected local or systemic hypersensitivity to quinolone antibiotics or
• tobramycin
• Viral illness within the last 30 days prior to screening
• Evidence of clinically relevant oral, cardiovascular, hematologic,gastrointestinal,
• hepatic, renal, endocrine, pulmonary, neurologic, psychiatric or skin disorder
• Pregnant or breast-feeding
• Males who are sexually active and of reproductive potential and whose female
• partners are of child-bearing potential (definition as above) who are not prepared to used adequate birth control, defined as a condom plus spermicidal gel or foam from
• screening, for the duration of the study, and up to 30 days after the last dose of
• study treatment. Surgical sterilization must be documented in the medical file.
• Use of any ciprofloxacin or related drugs prior to the recruitment interview, such that
• these drugs will have been ingested in the 4 weeks prior to the first dosing day
• Use of any other prescription medication (except oral contraceptives) during the 7
• days prior to study dosing unless approved by both the Principal Investigator and the
• sponsor
• Use of any over the counter product, herbal product, diet aid, hormone supplement, etc., within 7 days of study dosing unless approved by both the Principal Investigator and the sponsor
• Greater than normal alcohol consumption (i.e. more than 21 standard drinks per
• week for males, or more than 14 standard drinks per week for females)
• Ingestion of any poppy seeds within the 48 hours prior to the screening blood test
• (subjects will be advised by phone not to consume any poppy seed in this time
• period)
• Ingestion of any poppy seeds within the 48 hours prior to, or any alcohol, xanthines
• (i.e. tea, coffee, caffeine or cola drinks or chocolate) or grapefruit-containing foods or
• beverages within the 24 hours prior to, or any of the above within the first 24 hours
• after dosing
• Positive urine cotinine result at screening or at admission to clinic (details in
• Appendix 1)
• Positive breath alcohol result at screening or at admission to clinic (details in
• Appendix 1)
• Detection of any drug listed Appendix 1 (point 4a) in the urine drug screen at
• recruitment or any drug listed in Appendix 1 (point 4b) in the urine drug screen at
• admission, unless there is an explanation acceptable to the medical investigator (e.g.
• the subject has stated in advance that they consumed a prescription product which
• contained the detected drug) and/or the subject has a negative urine drug screen on
• retest by the pathology laboratory
• Failure to conform to the requirements of the protocol
• Vital signs outside the reference range and clinically significant
• Any clinically significant biochemical or hematological abnormality or any clinically
• significant abnormality in the urinalysis result
• Any vigorous exercise or strenuous activity within at least 48 hours before admission
• Subjects are requested to refrain as much as possible, from taking concomitant medications from recruitment until the conclusion of their participation in the study.
• Subjects with non-CF bronchiectasis must not have any of the following:
• Known or suspected local or systemic hypersensitivity to quinolone antibiotics or
• tobramycin.
• History of sputum culture or deep-throat cough swab (or BAL) culture yielding
• Burkholderia cepacia (B. cepacia), within 2 years prior to screening and/or sputum
• culture yielding B. cepacia at the Screening visit
• Hemoptysis exceeding 50 mL of blood from the respiratory tract at any time within 30 days prior to study drug administration
• Pregnant or breast-feeding
• Males who are sexually active and of reproductive potential and whose female
• partners are of child-bearing potential (definition as above) who are not prepared to used adequate birth control, defined as a condom plus spermicidal gel or foam from
• screening, for the duration of the study, and up to 30 days after the last dose of
• study treatment. Surgical sterilization must be documented in the medical file
• Use of any form of ciprofloxacin or other quinolone antibiotic within 14 days of study
• drug administration
• Participation in another clinical trial within 30 days of screening visit or receipt of an
• experimental therapy within 30 days prior to study dosing
• Initiation of treatment with chronic macrolide therapy, antibiotic therapy, hypertonic saline by inhalation, or inhaled corticosteroids within 14 days prior to study drug administration (subjects may be taking these therapies at the time of enrollment, but they must have initiated treatment more than 14 days prior to study drug administration)
• Subjects having an exacerbation during the screening process as defined as a
• requirement of inhaled, oral, or intravenous antibiotics prior to the first study dose will
• be excluded
• Use of any over-the-counter product, herbal product, diet aid, hormone supplement, etc., within 7 days prior to dosing unless approved by both the Principal Investigator and the Sponsor
• Subjects having a diagnosis of cystic fibrosis
• Subjects with clinically significant out of range laboratory values as determined by the investigator
• Ingestion of any poppy seeds within the 48 hours prior to the screening blood test
• (subjects will be advised by phone not to consume any poppy seed in this time
• period)
• Ingestion of any poppy seeds within the 48 hours prior to, or any alcohol, xanthines
• (i.e. tea, coffee, caffeine or cola drinks or chocolate) or grapefruit-containing foods or
• beverages within the 24 hours prior to, or any of the above within the first 24 hours
• after dosing
• Detection of any drug listed Appendix 1 (point 4a) in the urine drug screen at
• recruitment or any drug listed in Appendix 1 (point 4b) in the urine drug screen at
• admission, unless there is an explanation acceptable to the medical investigator (e.g.
• the subject has stated in advance that they consumed a prescription product which
• contained the detected drug) and/or the subject has a negative urine drug screen on
• retest by the pathology laboratory
• Donation >450 ml of blood within 8 weeks of first treatment dose
• Recent (1 year) history of drug or alcohol dependence
• Positive screening test for HIV antibodies, Hepatitis B surface antigen or Hepatitis C
• antibody
• Positive urine cotinine result at screening or at admission to clinic (details in
• Appendix 1)
• Positive breath alcohol result at screening or at admission to clinic (details in
• Appendix 1)
• Failure to conform to the requirements of the protocol
• Greater than normal alcohol consumption (i.e. more than 21 standard drinks per
• week for males, or more than 14 standard drinks per week for females)
• Vital signs outside the reference range and clinically significant