- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01966692
Sensitivity of Pharmacokinetics to Differences in Aerodynamic Particle Size Distribution
Evaluation of the Sensitivity of Pharmacokinetics to Differences in the Aerodynamic Particle Size Distribution of Three Different Formulations of Fluticasone Propionate Dry Powder Inhalers
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
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Gainesville, Florida, United States, 32610
- University of Florida
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Healthy male or female subjects aged 18 to 50 years (inclusive).
- Females will be eligible only if they are currently non-lactating and demonstrate a negative urine pregnancy test. Female subjects must be willing to use highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly e.g. no sexual intercourse, an intrauterine device (IUD), using contraceptive foam AND a condom (double-barrier).
- Body weight ranging from 50 to 100 kg, corresponding to a BMI of 18-29 kg/m2.
- Non-smoker for at least 12 months prior to study screening and a maximum smoking history of less than ten-pack years (i.e. the equivalent of one-pack per day for ten years).
- Healthy and free of significant abnormal findings as determined by medical history, physical examination, vital signs, laboratory tests (including serum cortisol at screening), complete blood count (CBC) with differential, urinalysis and basic metabolic panel.
- Ability to read, comprehend and sign the consent form.
- Ability and willingness to comply with all study procedures, discontinue and/or withhold medications as specified in the protocol, and attend scheduled study visits.
- No history of respiratory disease.
- Normal baseline spirometry as predicted for age, sex and height, including forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC) > 0.8.
- Healthy and without any pre-existing medical conditions.
Exclusion Criteria:
- Any history and/or conditions that might interfere with drug absorption, distribution, metabolism or excretion of FP, e.g., pre-existing lung and liver disease.
- Known or suspected sensitivity to Flonase (Fluticasone Propionate), Veramyst (Fluticasone Furoate), or related compounds in that class.
- Hypersensitivity to milk proteins or lactose (inactive ingredients in the formulation).
Having a history and/or currently having the medical condition in the opinion of medically accountable investigator and hence taking any medication for the following (including but not limited to):
4.1 Significant cardiac, dermatologic, gastrointestinal, hepatic, renal, hematological, neurological and psychiatric disease (determined by physical exam, CBC with differential, urinalysis, basic metabolic panel and medical history).
4.2 Presence of glaucoma, cataracts, ocular herpes simplex or carcinoma (other than basal cell).
4.3 Presence of tuberculosis and other respiratory diseases (including but not limited to intermittent or persistent asthma, emphysema and chronic bronchitis); or respiratory infection, common cold, sinusitis or ear infections.
- Current use of hormone replacement therapy (HRT), hormonal contraceptives and/or corticosteroid treatment within the last 2 months.
- Smoker during the last 1 year prior to study screening (self-report).
- Evidence of a positive pregnancy urine test for female volunteers or females who are pregnant or breast-feeding or are likely to become pregnant during the trial. Women of child-bearing potential may be included in the study if, in the opinion of the investigator, they are taking adequate contraceptive precautions as described above.
- Exposure to any investigational drug within 30 days of enrolment.
- Subjects who are unable to demonstrate proper inhalation of the test products.
- Subjects who have a history of anemia.
- Exposure to any medication that alters CYP3A4 activity within last 2 weeks (e.g.: azole antifungals, rifampin).
- Nausea, vomiting or diarrhoea within 7 days of dosing.
- Subjects who have donated 1 pint (450 mL) of blood or more within the previous 8 weeks prior to study administration.
- Any history or current drug or alcohol abuse, which would interfere with the subject's completion of the study and with adherence to the protocol.
- A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
- The subject is the student of the Principal Investigator (PI).
- Lack of willingness to have personal study related data collected, archived and transmitted according to the protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Fluticasone Propionate Formulation Sequence 1233*
Patients first received Fluticasone Propionate Drug formulation 1, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 2, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 3, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 3*. All Fluticasone Propionate Drug formulations were administered via Plastiape Monodose Dry Powder Inhaler, 500mcg single dose. Mass Median Aerodynamic Diameter (MMAD) for formulation 1 is 4.5 µm. MMAD for formulation 2 is 3.8 µm MMAD for formulation 3 is 3.7 µm. MMAD for formulation 3* is 3.7 µm. See Formulation Development in Detailed Description for details regarding differences in formulations |
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 set of capsules from the same batch of formulation 3 is given to the subject to assess the within-subject variability and to ensure that the study is sufficiently powered to show bioequivalence between two replicates of the same formulation. |
Active Comparator: Fluticasone Propionate Formulation Sequence 23*13
Patients first received Fluticasone Propionate Drug formulation 2, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 3*, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 1, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 3. All Fluticasone Propionate Drug formulations were administered via Plastiape Monodose Dry powder Inhaler, 500mcg single dose. MMAD for formulation 1 is 4.5 µm. MMAD for formulation 2 is 3.8 µm. MMAD for formulation 3 is 3.7 µm. MMAD for formulation 3* is 3.7 µm. See Formulation Development in Detailed Description for details regarding differences in formulations |
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 set of capsules from the same batch of formulation 3 is given to the subject to assess the within-subject variability and to ensure that the study is sufficiently powered to show bioequivalence between two replicates of the same formulation. |
Active Comparator: Fluticasone Propionate Formulation Sequence 313*2
Patients first received Fluticasone Propionate Drug formulation 3, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 1, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 3*, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 2. All Fluticasone Propionate Drug formulations were administered via Plastiape Monodose Dry Powder Inhaler, 500mcg single dose. MMAD for formulation 1 is 4.5 µm. MMAD for formulation 2 is 3.8 µm MMAD for formulation 3 is 3.7 µm. MMAD for formulation 3* is 3.7 µm. See Formulation Development in Detailed Description for details regarding differences in formulations |
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 set of capsules from the same batch of formulation 3 is given to the subject to assess the within-subject variability and to ensure that the study is sufficiently powered to show bioequivalence between two replicates of the same formulation. |
Active Comparator: Fluticasone Propionate Formulation Sequenct 3*321
Patients first received Fluticasone Propionate Drug formulation 3*, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 3, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 2, after a washout period of at least 5 days, they then received Fluticasone Propionate Drug formulation 1. All Fluticasone Propionate Drug formulations were administered via Plastiape Monodose Dry powder Inhaler, 500mcg single dose. * (The asterisk) A different set of capsules from the same batch of formulation 3 is given to the subject to assess the within-subject variability and to ensure that the study is sufficiently powered to show bioequivalence between two replicates of the same formulation. MMAD for formulation 1 is 4.5 µm. MMAD for formulation 2 is 3.8 µm MMAD for formulation 3 is 3.7 µm. MMAD for formulation 3* is 3.7 µm. |
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 set of capsules from the same batch of formulation 3 is given to the subject to assess the within-subject variability and to ensure that the study is sufficiently powered to show bioequivalence between two replicates of the same formulation. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Plasma Concentration-time Profile From Time 0 the Last Quantifiable Concentration (AUC0-last) With Dose Normalization
Time Frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
Area under the plasma concentration versus time curve from time zero (pre-dose) to the last quantifiable concentration after pulmonary dose (estimated from anatomical throats) normalization; measured as picograms multiplied by hours divided by milliliters (pg*h/mL).
|
Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
Maximum Plasma Concentration (Cmax) With Dose Normalization
Time Frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
Cmax measured as picograms divided by milliliters (pg/mL) after pulmonary dose (estimated from anatomical throats) normalization.
|
Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
Tmax measured as hours (h).
|
Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
Mean Residence Time (MRT)
Time Frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
MRT measured as hours (h)
|
Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
Elimination Half Life (t1/2)
Time Frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
t1/2 measured as hours (h)
|
Day 1 of Periods 1, 2, 3, and 4: pre-dose (15 minutes prior to the dosing), and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours (+/- 1 hour) post-dose
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Juergen Bulitta, PhD, University of Florida
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB201400464-need FDA approval
- 00079088 (Other Identifier: United States: Food and Drug Adminstration)
- HHSF223401610099C (Other Grant/Funding Number: US FOOD AND DRUG ADMN)
- OCR15966 (Other Identifier: University of Florida)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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