Lung Bioavailability and Total Systemic Exposure to Beclomethasone17MonoPropionate and Formoterol Across Two Strengths of NEXThaler Inhalation Powder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier:
NCT01738087
First received: November 15, 2012
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

The study is aimed to assess the dose proportional total systemic exposure (when the administration is without the activated charcoal) to B17MP (active metabolite of BDP) and its lung bioavailability (when the administration is with the activated charcoal) after single inhalation of CHF 1535 NEXThaler DPI at two dose strengths.

At the same time, the study will assess if the lung deposition and the total systemic exposure to Formoterol is affected by increasing doses of BDP.


Condition Intervention Phase
Asthmatic
Drug: NEXThaler 100/6 mcg DPI
Drug: Flixotide Accuhaler 500 mcg
Drug: NEXThaler 200/6 mcg DPI
Drug: NEXThaler placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Monocentric, Open, Randomized, 6-way Cross-over Clinical Pharmacology Study to Evaluate the Lung Bioavailability of BDP/B17MP and Formoterol and the Total Systemic Exposure Across Two Different Strengths of CHF 1535 NEXThaler Dry Powder Inhaler (Fixed Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate 100/6 Mcg and 200 Mcg) Administered With and Without Activated Charcoal in Adult Asthmatic Patients.

Resource links provided by NLM:


Further study details as provided by Chiesi Farmaceutici S.p.A.:

Primary Outcome Measures:
  • Formoterol AUC0-t and B17MP AUC0-t [ Time Frame: from predose until 12 hr post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • BDP pharmacokinetic (PK) parameters [ Time Frame: from predose until 12 hr post dose ] [ Designated as safety issue: No ]
    The following parameters will be evaluated: AUC0-t, AUC0-12h, AUC0-inf, Cmax, tmax, t1/2

  • Other PK parameter of B17MP and formoterol [ Time Frame: from predose until 12 hours postdose ] [ Designated as safety issue: No ]
    the following pharmacokinetic parameters will be evaluated: AUC0-12, AUCinf, Cmax, tmax, t1/2


Other Outcome Measures:
  • Plasma glucose [ Time Frame: from predose until 12 hours postdose ] [ Designated as safety issue: Yes ]
    the following parameters will be evaluated: AUC0-4h, AUC0-12h, Cmax and tmax

  • Heart rate (HR) [ Time Frame: from predose until 12 hours postdose ] [ Designated as safety issue: Yes ]
    the following parameters will be evaluated: HR AUC0-12/12h

  • Plasma cortisol [ Time Frame: from predose until 24 hours postdose ] [ Designated as safety issue: Yes ]
    the following parameters will be evaluated: AUC0-24, Cmin and tmin

  • Plasma potassium [ Time Frame: from predose until 12 hours postdose ] [ Designated as safety issue: Yes ]
    the following parameters will be evaluated: AUC0-4h, AUC0-12h, Cmin ad tmin

  • Systolic and Diastolic Blood Pressure (SBP and DBP) [ Time Frame: from predose until 12 hours postdose ] [ Designated as safety issue: Yes ]
    the following parameters will be evaluated: SBP AUC0-12/12h and DBP AUC0-12/12h


Enrollment: 30
Study Start Date: November 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NEXThaler 100/6 mcg DPI
Single dose (4 inhalations)of NEXThaler 100/6 mcg DPI: total dose 400/24 mcg
Drug: NEXThaler 100/6 mcg DPI
Other Name: Fixed combination of BDP plus formoterol fumarate
Experimental: NEXThaler 200/6 mcg DPI
Single dose (4 inhalations)of NEXThaler 200/6 mcg DPI: total dose: 800/24 mcg
Drug: NEXThaler 200/6 mcg DPI
Other Name: Fixed combination of BDP plus formoterol fumarate
Placebo Comparator: NEXThaler placebo
Single dose (4 inhalations)
Drug: NEXThaler placebo
Placebo comparator
Experimental: NEXThaler 100/6 mcg plus CB
Single dose (4 inhalations) NEXThaler 100/6 mcg administered with activated charcoal (Charcoal Block): total dose 400/24 mcg
Drug: NEXThaler 100/6 mcg DPI
Other Name: Fixed combination of BDP plus formoterol fumarate
Experimental: NEXThaler 200/6 mcg plus CB
Single dose (4 inhalations) NEXThaler 200/6 mcg administered with activated charcoal (Charcoal Block): total dose 800/24 mcg
Drug: NEXThaler 200/6 mcg DPI
Other Name: Fixed combination of BDP plus formoterol fumarate
Active Comparator: Flixotide Accuhaler 500 mcg
Single dose (2 inhalations) of fluticasone propionate
Drug: Flixotide Accuhaler 500 mcg
Active comparator
Other Name: Fluticasone Propionate

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of asthma as defined by Global Initiative for Asthma (GINA) 2011
  • Asthmatic patients already treated with low daily doses of Inhaled Corticosteroids (ICS) (eg budesonide or equivalent lower than 400 mcg/day) or low dose of ICS/Long Acting Beta2 Agonists (LABA) fixed combinations.
  • Patients with Forced Expiratory Volume in 1 sec (FEV1) >= 70 % of predicted values
  • Non or ex-smokers
  • Body Mass Index (BMI) >= 18.5 and <= 32 kg/m2

Exclusion Criteria:

  • Pregnant or lactating women unless using acceptable methods of contraception
  • Diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
  • History of near fatal asthma
  • Patients with abnormal QTcF at screening Visit
  • Hospitalization due to asthma exacerbation within 4 weeks prior to the screening visit or during the run-in period.
  • Lower respiratory tract infection within 4 weeks prior to the screening visit or during the run-in period.
  • History of drug addiction or excessive use of alcohol ;
  • Diagnosis of restrictive lung disease.
  • Patients treated with oral or parenteral corticosteroids in the previous 2 months before the screening visit (3 months for parenteral depot corticosteroids)
  • Significant medical history or any laboratory abnormality indicative of a significant underlying condition
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738087

Locations
United Kingdom
The Medicine Evaluation Unit
Manchester, United Kingdom, M23 9QZ
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
  More Information

No publications provided

Responsible Party: Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier: NCT01738087     History of Changes
Other Study ID Numbers: CCD-1205-PR-0087, 2012-002370-30
Study First Received: November 15, 2012
Last Updated: January 29, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Chiesi Farmaceutici S.p.A.:
patients
Adult

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Charcoal
Fluticasone
Beclomethasone
Formoterol
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014