Sensitivity of Pharmacokinetics to Differences in Aerodynamic Particle Size Distribution
Condition: Asthma
MeSH terms: Hypersensitivity
Study type: Interventional
Phase: Phase 1

Summary: 
      When a drug company first develops a drug, the company has to show the Food and Drug
      Administration (FDA) that the drug is safe and effective. If FDA concludes that the drug is
      safe and effective, FDA approves the drug. The company can then sell the drug, which the
      company does using "trade name." Only the drug company that developed the "trade name" drug
      is allowed to sell it. However, other drug companies can create their own version of the
      "trade name" drug, which usually happens after the patents for the "trade name" product run
      out. These drugs, often called "generic drugs," potentially will be less expensive for the
      patient. In order to sell generic drugs, drug companies must show that their generic version
      is the same as the "trade name" drug in a number of ways. For example, they generally have to
      show that their product is intended to be used to treat the same diseases or conditions, that
      it has the same label, and that the product has the same active ingredient as the "trade
      name" drug. The generic company also has to show that generic product is "bioequivalent" to
      the trade name drug, meaning that the generic product gets to the part of the body where the
      drug works at the same rate that the trade name drug does. How to show how much drug gets to
      the part of the body where it works, and how fast, depends on the type of product the drug
      is. The primary aim of this research study is to aid the FDA in finding methods to ensure
      that the versions of generic drugs that are inhaled (for example, drugs used to treat asthma)
      are bioequivalent to the trade name drug. As a part of the research study, pharmacokinetic
      (PK) studies (studies measuring drug levels in the blood over time after inhalation) will be
      done using three different versions of fluticasone propionate (FP, a drug routinely used in
      asthmatic patients) administered using a dry powder inhaler (DPI, an inhalation device that
      delivers the drug as a dry powder). The results from this study will help FDA ensure that
      generic products are the same as the trade name drugs.
    

Detailed description: 
      Formulation Development

      The aim of the pharmaceutical development was to manufacture three Dry powder Inhalation
      (DPI) formulations containing Fluticasone Propionate in an Plastiape Monodose DPI device,
      which provide distinct in vitro deposition patterns on a Next Generation Impactor. NGI is a
      high performance cascade impactor used to characterize aerosol particles by particle size. It
      is desirable to develop three formulations with the same emitted dose (ED), impactor size
      mass (ISM) but different mass median aerodynamic diameter (MMAD). Meeting these design
      criteria for the formulations would help to see if pharmacokinetic parameters are sensitive
      to regional differences in drug deposition whilst having the dose deposited in the lung from
      different formulations being the same.The three formulation developed are labeled Fluticasone
      Propionate Drug formulation 1 through 3.

      Study Procedures and scheduling

      The study is comprised of 5 visits in total - a screening visit and 4 treatment visits. At
      least 5 days should lapse between the treatment visits.

      Screening Visit During the screening visit, the inclusion and exclusion criteria will be
      reviewed to ensure the volunteer is appropriate for the study. The informed consent will be
      reviewed with the volunteer by a member of the study team and the volunteer will be
      encouraged to ask questions to ensure the volunteer has a good understanding of the study. If
      the volunteer is eligible and agrees to participate, the volunteer will be asked to sign the
      informed consent form prior to any study specific procedures including randomization. After
      the volunteer signs the informed consent, the volunteer will be interviewed and demographic
      data, medical history and concomitant medications will be collected and recorded. A physical
      examination will be performed after the vital sign measurements are obtained. A pregnancy
      test for female volunteers will be obtained. Spirometry testing and inhalation training will
      be performed by a qualified study clinician/investigator to ensure the suitability of
      volunteers. Laboratory tests including a Complete Blood Count (CBC), urinalysis and metabolic
      panel will be collected via venipuncture and processed in the lab. Screening tests will be
      performed within 14 days of treatment visit 1 and no later than 2 days before treatment visit
      1. All screening results will be evaluated by the study clinician/investigator against the
      inclusion/exclusion criteria to confirm the eligibility of the volunteers.

      Inhalation training: Inhalation training will be performed by a qualified study clinician at
      the screening visit and at each study visit. The training will be accomplished by
      instructions and subsequent inhalation via training devices containing empty capsules. The
      instructions on how to use the device correctly are similar to the Foradil Aerolizer DPI
      product information label. (http://www.rxlist.com/foradil-drug/medication-guide.htm )

      Treatment Visits 1, 2, 3 and 4 Eligible volunteers will be asked to return for treatment
      visit 1. A minimum period of 5 days should lapse between the subsequent treatment visits.
      Each treatment visit is scheduled for 28 hours over two days. The study will be conducted at
      the University of Florida (UF) CRC (Clinical Research Center). It is an outpatient study and
      the volunteer will be asked to come back the following day for the 24 hour blood sample. The
      volunteer will be asked to stay in an outpatient room during the treatment visit. The same
      activities are carried out at the other treatment visits.

      At each treatment visit, eligibility criteria will be reviewed and confirmed to ensure
      volunteer is appropriate for study. Changes in medical history including concomitant
      medications will be documented. Vital signs will be obtained. Inhalation training will be
      provided to the volunteers as mentioned in the section above. An IV catheter will be inserted
      in a vein located in the forearm region of the volunteer. The IV catheter is used to avoid
      multiple pricks while collecting blood samples. The IV catheter is not used for the
      administration of the drug. The volunteer inhales 5 times from a given inhaler during each
      treatment visit. Each inhaler will be used only once and by only one volunteer to ensure the
      volunteer's safety from infectious agents. The schedule below summarizes the procedures
      performed at the screening visit and a single treatment visit.

      Blood sample collection Blood samples will be drawn by inserting an indwelling catheter into
      the volunteer's median cubital vein in the forearm region. Blood samples will be taken 15
      minutes prior to the dosing of the product (pre-dose sample) and 5, 10, 15, 20, 30, 45, 60
      minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours post dosing. At each time point 9ml of
      blood sample will be collected of which the first 1ml will be discarded and the remaining 8
      ml will be stored in a vacutainer tube for plasma preparation and storage.
    

Intervention name(s): Fluticasone Propionate Formulation 1; Fluticasone Propionate Formulation 2; Fluticasone Propionate Formulation 3; Fluticasone Propionate Formulation 3*
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Fluticasone Propionate dry powder inhaler Formulation 1; Fluticasone Propionate dry powder inhaler Formulation 2; Fluticasone Propionate dry powder inhaler Formulation 3; Fluticasone Propionate dry powder inhaler Formulation 3*
*(The asterisk) A different batch of the formulation 3 is given to the patient to ensure that the study is sufficiently powered to show bioequivalence between two batches of the same formulation.
Intervention MeSH terms: Fluticasone; Xhance
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Other
Keywords: Bioequivalence; Fluticasone Propionate