An Open-Label, Randomized, Five-Period Cross-over, Single-dose Study to Compare Pharmacokinetics Profiles of Z7200 Medium Strength and Symbicort Turbohaler, With and Without Charcoal Blockade in Healthy Volunteers.
Overview
- Phase
- Phase 1
- Intervention
- Z7200 without oral activated charcoal
- Conditions
- Asthma
- Sponsor
- Zambon SpA
- Enrollment
- 91
- Locations
- 1
- Primary Endpoint
- AUC0-last of Budesonide With and Without Charcoal Blockade
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Brief Summary:
The primary objective was:
- to assess the bioequivalence of a single dose (two inhalations) of the test product compared to the reference product, with and without charcoal blockade.
The secondary objectives were:
- to assess the pharmacokinetic profile of budesonide and formoterol in plasma after a single dose (two inhalations) of the test product and the reference product, with and without charcoal blockade.
- to assess the safety and tolerability of the test product and the reference product, with and without charcoal blockade.
Detailed Description
This was a single center, open label, randomized, five-period crossover, single-dose study in healthy volunteers aged 18 to 45 years. A total of 90 volunteers were planned to be enrolled, with 9 subjects in each of the 10 treatment sequences. The study consisted of 5 treatment periods, each lasting approximately 48h, separated by a washout period of a minimum of 5 days. RS01 and/or Symbicort Turbohaler device use training was provided on Day -1 and Day 1 of each treatment period. Subjects were screened for eligibility to participate in the study -28 to -2 days prior to the first treatment period, and were randomized to one of 10 treatment sequences containing the following 5 treatment arms on Day 1 of the first treatment period: Treatment A: Z7200 without oral activated charcoal\* Treatment B1: Symbicort 1 without oral activated charcoal\* Treatment B2: Symbicort 2 without oral activated charcoal\* Treatment C: Z7200 with oral activated charcoal\*\* Treatment D: Symbicort with oral activated charcoal\*\* Subjects were admitted to the clinical unit at 8.00 on the morning of Day -1, and were dosed on the morning of Day 1 following an overnight fast (minimum of 8h). On Day 2, following collection of the 24-h PK blood sample, subjects were discharged. \* Subjects who received treatments A, B1 and B2 rinsed their mouth vigorously with 50 mL water for 3 to 5 sec immediately after the second inhalation. \*\* A charcoal blockade was used to prevent absorption from oropharyngeal and GI tract, in order to assess the pulmonary deposition of budesonide and formoterol, with periods performed without a charcoal blockade allowing the assessment of the total systemic exposure to the drug.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female 18 to 45 years of age.
- •If female, is currently not pregnant/breast feeding/ or attempting to become pregnant has a negative serum pregnancy test, or is of non-childbearing potential or is of child-bearing potential, willing to commit to using a consistent and acceptable method of birth control or is of child-bearing potential and not sexually active
- •Body mass index (BMI) of 18.0 to 32.0 kg/m² inclusive and a body weight ≥50 kg.
- •10 years or more past history of cigarette, \<=5 pack year
Exclusion Criteria
- •Forced Expiratory Volume in 1 sec (FEV1) value less than 80% of the predicted value and FEV1/FVC (Forced Vital Capacity) ratio \<0.
- •History or current evidence of a clinically significant disease or disorder capable of altering the absorption, metabolism, distribution or elimination of drugs.
- •History or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, haematological, neuropsychological, endocrine, gastrointestinal or pulmonary.
- •Presence of glaucoma, cataracts, ocular herpes simplex, malignancy, regardless of the clinical significance or current stability of the disease.
- •positive tests for Human Immunodeficiency Virus (HIV), Hepatitis B and Hepatitis C.
- •Bacterial or viral infection of the upper respiratory tract (including the common cold and flu), sinus, or middle ear within 2 weeks of dosing.
- •Lower respiratory tract infection/pneumonia within the past 3 months.
- •Presence of any disease or condition or regular concomitant treatment (including vitamins and herbal products) known to interfere with the absorption, distribution, metabolism or excretion of drugs.
- •Screening haemoglobin value of less than 1g/dL above the Lower Limit of Normality
- •History of recurrent vasovagal collapses.
Arms & Interventions
A-B1-B2-C-D
Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 days followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
A-B1-B2-C-D
Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 days followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
A-B1-B2-C-D
Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 days followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
A-B1-B2-C-D
Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 days followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
B1-C-A-D-B2
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
B1-C-A-D-B2
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
B1-C-A-D-B2
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
B1-C-A-D-B2
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
C-D-B1-B2-A
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
C-D-B1-B2-A
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
C-D-B1-B2-A
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
C-D-B1-B2-A
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
D-B2-C-A-B1
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
D-B2-C-A-B1
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
D-B2-C-A-B1
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
D-B2-C-A-B1
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
B2-A-D-B1-C
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
B2-A-D-B1-C
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
B2-A-D-B1-C
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
B2-A-D-B1-C
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
D-C-B2-B1-A
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
D-C-B2-B1-A
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
D-C-B2-B1-A
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
D-C-B2-B1-A
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
B2-D-A-C-B1
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
B2-D-A-C-B1
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
B2-D-A-C-B1
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
B2-D-A-C-B1
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
A-B2-B1-D-C
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
A-B2-B1-D-C
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
A-B2-B1-D-C
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
A-B2-B1-D-C
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
B1-A-C-B2-D
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
B1-A-C-B2-D
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
B1-A-C-B2-D
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
B1-A-C-B2-D
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
C-B1-D-A-B2
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 without oral activated charcoal
C-B1-D-A-B2
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler without oral activated charcoal
C-B1-D-A-B2
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Z7200 with oral activated charcoal
C-B1-D-A-B2
Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.
Intervention: Symbicort Turbohaler with oral activated charcoal
Outcomes
Primary Outcomes
AUC0-last of Budesonide With and Without Charcoal Blockade
Time Frame: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.
AUC0-last of Formoterol With and Without Charcoal Blockade
Time Frame: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.
Cmax of Budesonide With and Without Charcoal Blockade
Time Frame: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
Maximum plasma level of budesonide with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.
Cmax of Formoterol With and Without Charcoal Blockade
Time Frame: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
Maximum plasma level of formoterol with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.
Secondary Outcomes
- t1/2 for Budesonide With and Without Charcoal Blockade(0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min))
- t1/2 for Formoterol With and Without Charcoal Blockade(0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min))
- Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)(At 75 min (1.25 hours) post-dose)
- Change From Baseline in the Ratio of Forced Expiratory Volume in 1 Second to Forced Vital Capacity (FEV1/FVC)(At 75 min (1.25 hours) post-dose)
- AUC0-30 of Budesonide With and Without Charcoal Blockade.(0-30 min (0, 2, 5, 10, 15, 20, and 30 min))
- AUC0-30 of Formoterol With and Without Charcoal Blockade.(0-30 min (0, 2, 5, 10, 15, 20, and 30 min))
- AUC0-∞ of Budesonide With and Without Charcoal Blockade(0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min))
- AUC0-∞ of Formoterol With and Without Charcoal Blockade(0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min))
- Tmax for Budesonide With and Without Charcoal Blockade(0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min))
- Tmax for Formoterol With and Without Charcoal Blockade(0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min))
- Change From Baseline in Peak Expiratory Flow Rate (PEFR)(At 75 min (1.25 hours) post-dose)