Sensitivity of Pharmacokinetics to Differences in Particle Size Distribution of Suspension-based Nasal Sprays

NCT02588326 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: IRB201500381 - FHHSF223201310220COCR19758
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Currently FDA does not accept pharmacokinetic studies to show bioequivalence of locally-acting nasal suspension formulations. However, bioequivalence is defined as the absence of significant differences in pharmacokinetics of therapeutically equivalent drug products compared to the matching originally invented drug formulation. These there-called "generic drugs" are then interchangeable. Drug companies have to show that their generic version has the same active ingredient, the same label, is intended to be used for the same conditions or diseases and works at the same rate in the body. The aim of the study is to determine if pharmacokinetics is sensitive to differences in the particle size distribution of two different nasal suspension formulations of mometasone furoate during charcoal block. The result from this study will aid the FDA in finding methods to ensure that generic products are the same as the trade name drugs.

Conditions

Hypersensitivity

Keywords

Bioequivalence; Suspension nasal spray; Mometasone furoate; Pharmacokinetics; Particle size distribution

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration versus time curve (AUC) of mometasone furoate formulation 1

  15 min pre-dose and 5, 10, 15, 30, 45, 60 minutes and 1.5, 2, 3, 4, 6, 8, 10, 12 and 14 hours post-dose

• Area under the plasma concentration versus time curve (AUC) of mometasone furoate formulation 2

  15 min pre-dose and 5, 10, 15, 30, 45, 60 minutes and 1.5, 2, 3, 4, 6, 8, 10, 12 and 14 hours post-dose

Secondary Outcomes (2)

• Peak Plasma Concentration (Cmax) of mometasone furoate formulation 1

  15 min pre-dose and 5, 10, 15, 30, 45, 60 minutes and 1.5, 2, 3, 4, 6, 8, 10, 12 and 14 hours post-dose

• Peak Plasma Concentration (Cmax) of mometasone furoate formulation 2

  15 min pre-dose and 5, 10, 15, 30, 45, 60 minutes and 1.5, 2, 3, 4, 6, 8, 10, 12 and 14 hours post-dose

Study Arms (2)

MFF 1, then MFF 2

ACTIVE COMPARATOR

Mometasone furoate drug formulation (MFF) 1 will be administered by suspension-based nasal spray. After a wash out period then Mometasone furoate drug formulation (MFF) 2 will be administered by suspension-based nasal spray. All formulations will be a 200 mcg single dose.

Drug: Mometasone furoate drug formulation (MFF) 1; Drug: Mometasone furoate drug formulation (MFF) 2

MFF 2, then MFF 1

ACTIVE COMPARATOR

Mometasone furoate drug formulation (MFF) 2 will be administered by suspension-based nasal spray. After a wash out period then Mometasone furoate drug formulation (MFF) 1 will be administered by suspension-based nasal spray. All formulations will be a 200 mcg single dose.

Drug: Mometasone furoate drug formulation (MFF) 1; Drug: Mometasone furoate drug formulation (MFF) 2

Interventions

Mometasone furoate drug formulation (MFF) 1 DRUG

Mometasone furoate drug formulation (MFF) 1 will be administered by suspension-based nasal spray.

Also known as: Nasonex re-engineered version

MFF 1, then MFF 2; MFF 2, then MFF 1

Mometasone furoate drug formulation (MFF) 2 DRUG

Mometasone furoate drug formulation (MFF) 2 will be administered by suspension-based nasal spray.

Also known as: Nasonex re-engineered version

MFF 1, then MFF 2; MFF 2, then MFF 1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects aged 18 to 50 years (inclusive).
• Body mass index (BMI) between 18.5 and 30.0 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).
• Free of significant abnormal findings as determined by medical history, physical examination, vital signs, and 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 informed 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 major respiratory disease (such as cystic fibrosis or COPD).
• Able to demonstrate correct nasal spray technique at screening.

You may not qualify if:

• Any history and/or conditions that might interfere with drug absorption, distribution, metabolism or excretion of MF, e.g., preexisting lung and liver disease.
• Known or suspected sensitivity or allergic reaction to MF, or related compounds in that class, or one of the excipients, or to activated charcoal.
• Known or suspected sensitivity to benzalkonium chloride or to products containing this salt.
• 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):
• 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).
• Presence of glaucoma, cataracts, ocular herpes simplex or carcinoma (other than basal cell).
• 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.
• Based on the medical interview, physical examination or screening investigations, subject is unfit for the study in the opinion of the medically accountable investigator.
• Current use of hormone replacement therapy (HRT), hormonal contraceptives (oral, implants, or IUDs) and/or use corticosteroid within the last 2 month.
• Atrophic rhinitis or rhinitis medicamentosa within the last 60 days.
• Any history of nasal surgery or known clinically relevant abnormalities, such as rhinitis medicamentosa, polyposis, septum deviation with clinical symptoms, recent nasal trauma, or nasal structural abnormalities.
• History of recurrent epistaxis, or any epistaxis requiring medical intervention.
• Known perennial airway allergies or vasomotor rhinitis.
• Known seasonal airway allergies within the last six weeks prior to the start of the study or seasonal airway allergies that likely become acute during the study period. Subjects may be included in the study, if e.g. a mild or unlikely seasonal airway allergy does not interfere with the nasal absorption of mometasone furoate in the opinion of the medically accountable investigator and principal investigator.
• Acute sinusitis within the last six weeks prior to enrollment.

Sponsors & Collaborators

• University of Florida: lead
• Food and Drug Administration (FDA): collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Department of Pharmaceutics, University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Hypersensitivity

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Jurgen Bulitta, PhD

  University of Florida jbulitta@cop.ufl.edu

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2015
• First Posted: October 27, 2015
• Study Start: September 21, 2018
• Primary Completion: July 8, 2020
• Study Completion: April 16, 2021
• Last Updated: November 16, 2021

Record last verified: 2021-11

Locations

US (1)